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Fulltext Notes on Amanita section Validae in Hainan Island, China

Huang T, Su LJ, Zeng NK, Lee SML, Lee SS, Thi BK, et al.

Front Microbiol, 2022;13:1087756.
PMID: 36741898 DOI: 10.3389/fmicb.2022.1087756

Hainan is the second largest island in China with the most extensive and well-preserved tropical forests and is also the largest island of the Indo Burma Biodiversity Hotspot. It provides in situ conservation for the unique ecosystem of the island. Recent studies have shown that there are diverse fungal species in Hainan. In this study, about 40 collections of the genus Amanita have been studied based on the morphology and molecular systematics, including 35 Chinese specimens (24 from Hainan, and eleven from other regions) and three specimens from other countries (Singapore and Malaysia). In total, five new species belonging to Amanita section Validae are described: A. cacaina, A. parvigrisea, A. pseudofritillaria, A. pseudosculpta, and A. yangii. Amanita parvifritillaria is recorded for the first time in Hainan. It is also the first report of this fungus occurring, outside Yunnan Province, China. Among the five new species, two are unique in this section because of the appendiculate pileus margin and the absence of an annulus. Based on these new findings, the diagnosis of the section Validae should be slightly modified to include a few species with appendiculate margin and the lack of annulus.
Fulltext Investigating the antidiabetic efficacy of dairy-derived Lacticaseibacillus paracasei probiotic strains: modulating α-amylase and α-glucosidase enzyme functions

Huligere SS, Kumari V B C, Desai SM, Wong LS, Firdose N, Ramu R

Front Microbiol, 2023;14:1288487.
PMID: 38111646 DOI: 10.3389/fmicb.2023.1288487

The current study aims to evaluate and characterize the probiotic andantidiabetic properties of lactic acid bacteria (LAB) obtained from milk and other dairy-based products. The strains were tested physiologically, biochemically, and molecularly. Based on biochemical tests and 16S rRNA gene amplification and sequencing, all three isolates RAMULAB18, RAMULAB19, and RAMULAB53 were identified as Lacticaseibacillus paracasei with homology similarity of more than 98%. The inhibitory potential of each isolate against carbohydrate hydrolysis enzymes (α-amylase and α-glucosidase) was assessed using three different preparations of RAMULAB (RL) isolates: the supernatant (RL-CS), intact cells (RL-IC), and cell-free extraction (RL-CE). Additionally, the isolate was evaluated for its antioxidant activity against free radicals (DPPH and ABTS). The strain's RL-CS, RL-CE, and RL-IC inhibited α-amylase (17.25 to 55.42%), α-glucosidase (15.08-59.55%), DPPH (56.42-87.45%), and ABTS (46.35-78.45%) enzymes differently. With the highest survival rate (>98%) toward tolerance to gastrointestinal conditions, hydrophobicity (>42.18%), aggregation (>74.21%), as well as attachment to an individual's colorectal cancer cell line (HT-29) (>64.98%), human buccal and chicken crop epithelial cells, all three isolates exhibited extensive results. All three isolates exhibited high resistance toward antibiotics (methicillin, kanamycin, cefixime, and vancomycin), and other assays such as antibacterial, DNase, hemolytic, and gelatinase were performed for safety assessment. Results suggest that the LAB described are valuable candidates for their significant health benefits and that they can also be utilized as a beginning or bio-preservative tradition in the food, agriculture, and pharmaceutical sectors. The LAB isolates are excellent in vitro probiotic applicants and yet additional in vivo testing is required.
Fulltext Deletion of Salmonella enterica serovar Typhi tolC reduces bacterial adhesion and invasion toward host cells

Hussain A, Ong EBB, Balaram P, Ismail A, Kien PK

Front Microbiol, 2023;14:1301478.
PMID: 38029101 DOI: 10.3389/fmicb.2023.1301478

BACKGROUND: S. Typhi is a Gram-negative bacterium that causes typhoid fever in humans. Its virulence depends on the TolC outer membrane pump, which expels toxic compounds and antibiotics. However, the role of TolC in the host cell adhesion and invasion by S. Typhi is unclear.
OBJECTIVE: We aimed to investigate how deleting the tolC affects the adhesion and invasion of HT-29 epithelial and THP-1 macrophage cells by S. Typhi in vitro.
METHODS: We compared the adhesion and invasion rates of the wild-type and the tolC mutant strains of S. Typhi using in vitro adhesion and invasion assays. We also measured the expression levels of SPI-1 genes (invF, sipA, sipC, and sipD) using quantitative PCR.
RESULTS: We found that the tolC mutant showed a significant reduction in adhesion and invasion compared to the wild-type strain in both cell types. We also observed that the expression of SPI-1 genes was downregulated in the tolC mutant.
DISCUSSION: Our results suggest that TolC modulates the expression of SPI-1 genes and facilitates the adhesion and invasion of host cells by S. Typhi. Our study provides new insights into the molecular mechanisms of S. Typhi pathogenesis and antibiotic resistance. However, our study is limited by the use of in vitro models and does not reflect the complex interactions between S. Typhi and host cells in vivo.
Postmortem skin microbiome signatures associated with human cadavers within the first 12 h at the morgue

Iancu L, Muslim A, Aazmi S, Jitaru V

Front Microbiol, 2023;14:1234254.
PMID: 37564294 DOI: 10.3389/fmicb.2023.1234254

INTRODUCTION: Forensic microbiome studies expanded during the last decade, aiming to identify putative bacterial biomarkers to be used for the postmortem interval (PMI) estimation. Bacterial diversity and dynamics during decomposition are influenced by each individual's micro and macroenvironment, ante and postmortem conditions, varying across body sites and time. The skin, the largest organ of the human body, hosts a diverse microbial diversity, representing the first line of defense of a living individual. Targeting the investigation of the postmortem skin microbiome could help understanding the role of microbes during decomposition, and association with the ante and postmortem conditions.
METHODS: The current study aimed to identify the postmortem skin microbiome signatures associated with eight human bodies, received at the Institute of Legal Medicine Iasi, Romania, during April and May 2021. A total of 162 samples (including triplicate) representing face and hands skin microbiome were investigated via Illumina MiSeq, upon arrival at the morgue (T0) and after 12 hours (T1).
RESULTS: The taxonomic characteristics of the skin microbiota varied across different body sites. However, there were no significant differences in taxonomic profiles between collection time, T0 and T1, except for some dynamic changes in the abundance of dominant bacteria. Moreover, different microbial signatures have been associated with a specific cause of death, such as cardiovascular disease, while an elevated blood alcohol level could be associated with a decrease in bacterial richness and diversity.
DISCUSSION: The places where the bodies were discovered seemed to play an important role in explaining the bacterial diversity composition. This study shows promising results towards finding common postmortem bacterial signatures associated with human cadavers within the first 12h at the morgue.
Fulltext Role of microbial electrosynthesis system in CO2 capture and conversion: a recent advancement toward cathode development

Ibrahim I, Salehmin MNI, Balachandran K, Hil Me MF, Loh KS, Abu Bakar MH, et al.

Front Microbiol, 2023;14:1192187.
PMID: 37520357 DOI: 10.3389/fmicb.2023.1192187

Microbial electrosynthesis (MES) is an emerging electrochemical technology currently being researched as a CO2 sequestration method to address climate change. MES can convert CO2 from pollution or waste materials into various carbon compounds with low energy requirements using electrogenic microbes as biocatalysts. However, the critical component in this technology, the cathode, still needs to perform more effectively than other conventional CO2 reduction methods because of poor selectivity, complex metabolism pathways of microbes, and high material cost. These characteristics lead to the weak interactions of microbes and cathode electrocatalytic activities. These approaches range from cathode modification using conventional engineering approaches to new fabrication methods. Aside from cathode development, the operating procedure also plays a critical function and strategy to optimize electrosynthesis production in reducing operating costs, such as hybridization and integration of MES. If this technology could be realized, it would offer a new way to utilize excess CO2 from industries and generate profitable commodities in the future to replace fossil fuel-derived products. In recent years, several potential approaches have been tested and studied to boost the capabilities of CO2-reducing bio-cathodes regarding surface morphology, current density, and biocompatibility, which would be further elaborated. This compilation aims to showcase that the achievements of MES have significantly improved and the future direction this is going with some recommendations. Highlights - MES approach in carbon sequestration using the biotic component.- The role of microbes as biocatalysts in MES and their metabolic pathways are discussed.- Methods and materials used to modify biocathode for enhancing CO2 reduction are presented.
Fulltext PDR Transporter ABC1 Is Involved in the Innate Azole Resistance of the Human Fungal Pathogen Fusarium keratoplasticum

James JE, Lamping E, Santhanam J, Cannon RD

Front Microbiol, 2021;12:673206.
PMID: 34149660 DOI: 10.3389/fmicb.2021.673206

Fusarium keratoplasticum is arguably the most common Fusarium solani species complex (FSSC) species associated with human infections. Invasive fusariosis is a life-threatening fungal infection that is difficult to treat with conventional azole antifungals. Azole drug resistance is often caused by the increased expression of pleiotropic drug resistance (PDR) ATP-binding cassette (ABC) transporters of the ABCG sub-family. Most investigations of Fusarium ABC transporters associated with azole antifungal drug resistance are limited to plant pathogens. Through the manual curation of the entire ABCG protein family of four FSSC species including the fully annotated genome of the plant pathogen Nectria haematococca we identified PDR transporters ABC1 and ABC2 as the efflux pump candidates most likely to be associated with the innate azole resistance phenotype of Fusarium keratoplasticum. An initial investigation of the transcriptional response of logarithmic phase F. keratoplasticum cells to 16 mg/L voriconazole confirmed strong upregulation (372-fold) of ABC1 while ABC2 mRNA levels were unaffected by voriconazole exposure over a 4 h time-period. Overexpression of F. keratoplasticum ABC1 and ABC2 in the genetically modified Saccharomyces cerevisiae host ADΔΔ caused up to ∼1,024-fold increased resistance to a number of xenobiotics, including azole antifungals. Although ABC1 and ABC2 were only moderately (20% and 10%, respectively) expressed compared to the Candida albicans multidrug efflux pump CDR1, overexpression of F. keratoplasticum ABC1 caused even higher resistance levels to certain xenobiotics (e.g., rhodamine 6G and nigericin) than CDR1. Our investigations suggest an important role for ABC1 orthologues in the innate azole resistance phenotype of FSSC species.
Fulltext A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica

James JE, Lamping E, Santhanam J, Milne TJ, Abd Razak MF, Zakaria L, et al.

Front Microbiol, 2020;11:272.
PMID: 32296397 DOI: 10.3389/fmicb.2020.00272

In the fungal pathogen Aspergillus fumigatus, resistance to azole antifungals is often linked to mutations in CYP51A, a gene that encodes the azole antifungal drug target lanosterol 14α-demethylase. The aim of this study was to investigate whether similar changes could be associated with azole resistance in a Malaysian Fusarium solani species complex (FSSC) isolate collection. Most (11 of 15) clinical FSSC isolates were Neocosmospora keratoplastica and the majority (6 of 10) of environmental isolates were Neocosmospora suttoniana strains. All 25 FSSC isolates had high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole, low MICs for amphotericin B, and various (1 to >32 mg/l) voriconazole susceptibilities. There was a tight association between a 23 bp CYP51A promoter deletion and high (>32 mg/l) voriconazole MICs; of 19 FSSC strains sequenced, nine isolates had voriconazole MICs > 32 mg/l, and they all contained the 23 bp CYP51A promoter deletion, although it was absent in the ten remaining isolates with low (≤12 mg/l) voriconazole MICs. Surprisingly, this association between voriconazole resistance and the 23 bp CYP51A promoter deletion held true across species boundaries. It was randomly distributed within and across species boundaries and both types of FSSC isolates were found among environmental and clinical isolates. Three randomly selected N. keratoplastica isolates with low (≤8 mg/l) voriconazole MICs had significantly lower (1.3-7.5 times) CYP51A mRNA expression levels than three randomly selected N. keratoplastica isolates with high (>32 mg/l) voriconazole MICs. CYP51A expression levels, however, were equally strongly induced (~6,500-fold) by voriconazole in two representative strains reaching levels, after 80 min of induction, that were comparable to those of CYP51B. Our results suggest that FSSC isolates with high voriconazole MICs have a 23 bp CYP51A promoter deletion that provides a potentially useful marker for voriconazole resistance in FSSC isolates. Early detection of possible voriconazole resistance is critical for choosing the correct treatment option for patients with invasive fusariosis.
Editorial: Biofilms: multi-species community interactions

Joshi SJ, Ray RR, Erlich GD, Edinur HA

Front Microbiol, 2023;14:1191406.
PMID: 37303794 DOI: 10.3389/fmicb.2023.1191406
Fulltext Recent Understanding of Soil Acidobacteria and Their Ecological Significance: A Critical Review

Kalam S, Basu A, Ahmad I, Sayyed RZ, El-Enshasy HA, Dailin DJ, et al.

Front Microbiol, 2020;11:580024.
PMID: 33193209 DOI: 10.3389/fmicb.2020.580024

Acidobacteria represents an underrepresented soil bacterial phylum whose members are pervasive and copiously distributed across nearly all ecosystems. Acidobacterial sequences are abundant in soils and represent a significant fraction of soil microbial community. Being recalcitrant and difficult-to-cultivate under laboratory conditions, holistic, polyphasic approaches are required to study these refractive bacteria extensively. Acidobacteria possesses an inventory of genes involved in diverse metabolic pathways, as evidenced by their pan-genomic profiles. Because of their preponderance and ubiquity in the soil, speculations have been made regarding their dynamic roles in vital ecological processes viz., regulation of biogeochemical cycles, decomposition of biopolymers, exopolysaccharide secretion, and plant growth promotion. These bacteria are expected to have genes that might help in survival and competitive colonization in the rhizosphere, leading to the establishment of beneficial relationships with plants. Exploration of these genetic attributes and more in-depth insights into the belowground mechanics and dynamics would lead to a better understanding of the functions and ecological significance of this enigmatic phylum in the soil-plant environment. This review is an effort to provide a recent update into the diversity of genes in Acidobacteria useful for characterization, understanding ecological roles, and future biotechnological perspectives.
Fulltext Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach

Kaliaperumal K, Salendra L, Liu Y, Ju Z, Sahu SK, Elumalai S, et al.

Front Microbiol, 2023;14:1216928.
PMID: 37849927 DOI: 10.3389/fmicb.2023.1216928

INTRODUCTION: Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties.
METHODS: An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening.
RESULTS: Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain.
DISCUSSION: We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.
Fulltext Lessons Learned From Failures and Success Stories of HIV Breakthroughs: Are We Getting Closer to an HIV Cure?

Kalidasan V, Theva Das K

Front Microbiol, 2020;11:46.
PMID: 32082282 DOI: 10.3389/fmicb.2020.00046

There is a continuous search for an HIV cure as the success of ART in blocking HIV replication and the role of CD4+ T cells in HIV pathogenesis and immunity do not entirely eradicate HIV. The Berlin patient, who is virus-free, serves as the best model for a 'sterilizing cure' and many experts are trying to mimic this approach in other patients. Although failures were reported among Boston and Essen patients, the setbacks have provided valuable lessons to strengthen cure strategies. Following the Berlin patient, two more patients known as London and Düsseldorf patients might be the second and third person to be cured of HIV. In all the cases, the patients underwent chemotherapy regimen due to malignancy and hematopoietic stem cell transplantation (HSCT) which required matching donors for CCR5Δ32 mutation - an approach that may not always be feasible. The emergence of newer technologies, such as long-acting slow-effective release ART (LASER ART) and CRISPR/Cas9 could potentially overcome the barriers due to HIV latency and persistency and eliminate the need for CCR5Δ32 mutation donor. Appreciating the failure and success stories learned from these HIV breakthroughs would provide some insight for future HIV eradication and cure strategies.
Fulltext Effect of different levels of EDTA on phytoextraction of heavy metal and growth of Brassica juncea L

Kamal MA, Perveen K, Khan F, Sayyed RZ, Hock OG, Bhatt SC, et al.

Front Microbiol, 2023;14:1228117.
PMID: 37601347 DOI: 10.3389/fmicb.2023.1228117

Heavy metal pollution of soil is a major concern due to its non-biodegradable nature, bioaccumulation, and persistence in the environment. To explore the probable function of EDTA in ameliorating heavy metal toxicity and achieve the sustainable development goal (SDG), Brassica juncea L. seedlings were treated with different concentrations of EDTA (0, 1.0, 2.0, 3.0, and 4.0 mM Kg-1) in heavy metal-polluted soil. Plant samples were collected 60 days after sowing; photosynthetic pigments, H2O2, monoaldehyde (MDA), antioxidant enzymes, and ascorbic acid content, as well as plant biomass, were estimated in plants. Soil and plant samples were also examined for the concentrations of Cd, Cr, Pb, and Hg. Moreover, values of the phytoremediation factor were utilized to assess the accumulation capacity of heavy metals by B. juncea under EDTA treatments. In the absence of EDTA, B. juncea seedlings accrued heavy metals in their roots and shoots in a concentration-dependent manner. However, the highest biomass of plants (roots and shoots) was recorded with the application of 2 mM kg-1 EDTA. Moreover, high levels (above 3 mM kg-1) of EDTA concentration have reduced the biomass of plants (roots and shoots), photosynthetic area, and chlorophyll content. The effect of EDTA levels on photosynthetic pigments (chlorophyll a and b) revealed that with an increment in EDTA concentration, accumulation of heavy metals was also increased in the plant, subsequently decreasing the chlorophyll a and b concentration in the plant. TLF was found to be in the order Pb> Hg> Zn> and >Ni, while TF was found to be in the order Hg>Zn>Ni>Pb, and the best dose was 3 mM kg-1 EDTA for Hg and 4 mM kg-1 for Pb, Ni, and Zn. Furthermore, hyperaccumulation of heavy metals enhanced the generation of hydrogen peroxide (H2O2), superoxide anions (O2•-), and lipid peroxidation. It also interrupts mechanisms of the antioxidant defense system. Furthermore, heavy metal stress reduced plant growth, biomass, and chlorophyll (chl) content. These findings suggest that the exogenous addition of EDTA to the heavy metal-treated seedlings increases the bioavailability of heavy metals for phytoextraction and decreases heavy metal-induced oxidative injuries by restricting heavy metal uptake and components of their antioxidant defense systems.
Fulltext Exploration of Microbial Factories for Synthesis of Nanoparticles - A Sustainable Approach for Bioremediation of Environmental Contaminants

Kapoor RT, Salvadori MR, Rafatullah M, Siddiqui MR, Khan MA, Alshareef SA

Front Microbiol, 2021;12:658294.
PMID: 34149647 DOI: 10.3389/fmicb.2021.658294

The nanomaterials synthesis is an intensifying research field due to their wide applications. The high surface-to-volume ratio of nanoparticles and quick interaction capacity with different particles make them as an attractive tool in different areas. Conventional physical and chemical procedures for development of metal nanoparticles become outmoded due to extensive production method, energy expenditure and generation of toxic by-products which causes significant risks to the human health and environment. Hence, there is a growing requirement to search substitute, non-expensive, reliable, biocompatible and environmental friendly methods for development of nanoparticles. The nanoparticles synthesis by microorganisms has gained significant interest due to their potential to synthesize nanoparticles in various sizes, shape and composition with different physico-chemical properties. Microbes can be widely applied for nanoparticles production due to easy handling and processing, requirement of low-cost medium such as agro-wastes, simple scaling up, economic viability with the ability of adsorbing and reducing metal ions into nanoparticles through metabolic processes. Biogenic synthesis of nanoparticles offers clean, non-toxic, environmentally benign and sustainable approach in which renewable materials can be used for metal reduction and nanoparticle stabilization. Nanomaterials synthesized through microbes can be used as a pollution abatement tool as they also contain multiple functional groups that can easily target pollutants for efficient bioremediation and promotes environmental cleanup. The objective of the present review is to highlight the significance of micro-organisms like bacteria, actinomycetes, filamentous fungi, yeast, algae and viruses for nanoparticles synthesis and advantages of microbial approaches for elimination of heavy metals, dyes and wastewater treatment.
Fulltext The occurrence and molecular detection of mcr-1 and mcr-5 genes in Enterobacteriaceae isolated from poultry and poultry meats in Malaysia

Karim MR, Zakaria Z, Hassan L, Faiz NM, Ahmad NI

Front Microbiol, 2023;14:1208314.
PMID: 37601372 DOI: 10.3389/fmicb.2023.1208314

The advent of antimicrobials-resistant (AMR), including colistin-resistant bacteria, poses a significant challenge to animal and human health, food safety, socio-economic growth, and the global environment. This study aimed to ascertain the colistin resistance prevalence and molecular mechanisms of colistin resistance in Enterobacteriaceae. The colistin resistance was determined using broth microdilution assay, PCR; and Sanger sequencing of mcr genes responsible for colistin resistance in Enterobacteriaceae (n = 627), including Escherichia coli (436), Salmonella spp. (n = 140), and Klebsiella pneumoniae (n = 51), obtained from chicken and chicken meats. Out of 627 Enterobacteriaceae, 8.6% of isolates exhibited colistin resistance phenotypically. Among these colistin resistant isolates, 9.3% (n = 37) were isolated from chicken meat, 7.2% (n = 11) from the cloacal swab of chicken and 7.9% (n = 6) from the litter samples. Overall, 12.96% of colistin-resistant isolates were positive with mcr genes, in which mcr-1 and mcr-5 genes were determined in 11.11% and 1.85% of colistin-resistant isolates, respectively. The E. coli isolates obtained from chicken meats, cloacal swabs and litter samples were found positive for mcr-1, and Salmonella spp. originated from the chicken meat sample was observed with mcr-5, whereas no mcr genes were observed in K. pneumoniae strains isolated from any of the collected samples. The other colistin resistance genes, including mcr-2, mcr-3, mcr-4, mcr-6, mcr-7, mcr-8, mcr-9, and mcr-10 were not detected in the studied samples. The mcr-1 and mcr-5 genes were sequenced and found to be 100% identical to the mcr-1 and mcr-5 gene sequences available in the NCBI database. This is the first report of colistin resistance mcr-5 gene in Malaysia which could portend the emergence of mcr-5 harboring bacterial strains for infection. Further studies are needed to characterize the mr-5 harbouring bacteria for the determination of plasmid associated with mcr-5 gene.
Fulltext Streptomyces as a Prominent Resource of Future Anti-MRSA Drugs

Kemung HM, Tan LT, Khan TM, Chan KG, Pusparajah P, Goh BH, et al.

Front Microbiol, 2018;9:2221.
PMID: 30319563 DOI: 10.3389/fmicb.2018.02221

Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.
Fulltext Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia

Khaw YS, Chan YF, Jafar FL, Othman N, Chee HY

Front Microbiol, 2016;7:543.
PMID: 27199901 DOI: 10.3389/fmicb.2016.00543

Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection.
Fulltext The Human Gut Microbiome - A Potential Controller of Wellness and Disease

Kho ZY, Lal SK

Front Microbiol, 2018;9:1835.
PMID: 30154767 DOI: 10.3389/fmicb.2018.01835

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
Fulltext Amoxicillin-docosahexaenoic acid encapsulated chitosan-alginate nanoparticles as a delivery system with enhanced biocidal activities against Helicobacter pylori and improved ulcer healing

Khoshnood S, Negahdari B, Kaviar VH, Sadeghifard N, Abdullah MA, El-Shazly M, et al.

Front Microbiol, 2023;14:1083330.
PMID: 36846798 DOI: 10.3389/fmicb.2023.1083330

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat's stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.
Proteomics Analysis Revealed that Crosstalk between Helicobacter pylori and Streptococcus mitis May Enhance Bacterial Survival and Reduces Carcinogenesis

Khosravi Y, Loke MF, Goh KL, Vadivelu J

Front Microbiol, 2016;7:1462.
PMID: 27695448

Helicobacter pylori is the dominant species of the human gastric microbiota and is present in the stomach of more than half of the human population worldwide. Colonization by H. pylori causes persistent inflammatory response and H. pylori-induced gastritis is the strongest singular risk factor for the development of gastric adenocarcinoma. However, only a small proportion of infected individuals develop malignancy. Besides H. pylori, other microbial species have also been shown to be related to gastritis. We previously reported that interspecies microbial interaction between H. pylori and S. mitis resulted in alteration of their metabolite profiles. In this study, we followed up by analyzing the changing protein profiles of H. pylori and S. mitis by LC/Q-TOF mass spectrometry to understand the different response of the two bacterial species in a multi-species micro-environment. Differentially-expressed proteins in mono- and co-cultures could be mapped into 18 biological pathways. The number of proteins involve in RNA degradation, nucleotide excision repair, mismatch repair, and lipopolysaccharide (LPS) biosynthesis were increased in co-cultured H. pylori. On the other hand, fewer proteins involve in citrate cycle, glycolysis/ gluconeogenesis, aminoacyl-tRNA biosynthesis, translation, metabolism, and cell signaling were detected in co-cultured H. pylori. This is consistent with our previous observation that in the presence of S. mitis, H. pylori was transformed to coccoid. Interestingly, phosphoglycerate kinase (PGK), a major enzyme used in glycolysis, was found in abundance in co-cultured S. mitis and this may have enhanced the survival of S. mitis in the multi-species microenvironment. On the other hand, thioredoxin (TrxA) and other redox-regulating enzymes of H. pylori were less abundant in co-culture possibly suggesting reduced oxidative stress. Oxidative stress plays an important role in tissue damage and carcinogenesis. Using the in vitro co-culture model, this study emphasized the possibility that pathogen-microbiota interaction may have a protective effect against H. pylori-associated carcinogenesis.
Fulltext Halotolerant Plant Growth-Promoting Rhizobacteria Isolated From Saline Soil Improve Nitrogen Fixation and Alleviate Salt Stress in Rice Plants

Khumairah FH, Setiawati MR, Fitriatin BN, Simarmata T, Alfaraj S, Ansari MJ, et al.

Front Microbiol, 2022;13:905210.
PMID: 35770168 DOI: 10.3389/fmicb.2022.905210

Salinity is one of the most damaging abiotic stresses due to climate change impacts that affect the growth and yield of crops, especially in lowland rice fields and coastal areas. This research aimed to isolate potential halotolerant plant growth-promoting rhizobacteria from different rhizo-microbiome and use them as effective bioinoculants to improve rice growth under salinity stress conditions. Bioassay using rice seedlings was performed in a randomized block design consisting of 16 treatments (control and 15 bacterial isolates) with three replications. Results revealed that isolates S3, S5, and S6 gave higher shoot height, root length, and plant dry weight compared with control (without isolates). Based on molecular characteristics, isolates S3 and S5 were identified as Pseudomonas stutzeri and Klebsiella pneumonia. These isolates were able to promote rice growth under salinity stress conditions as halotolerant plant growth-promoting rhizobacteria. These three potent isolates were found to produce indole-3-acetic acid and nitrogenase.

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