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Cervical cancer burden, status of implementation and challenges of cervical cancer screening in Association of Southeast Asian Nations (ASEAN) countries

Zhao S, Huang L, Basu P, Domingo EJ, Supakarapongkul W, Ling WY, et al.

Cancer Lett, 2022 Jan 28;525:22-32.
PMID: 34728309 DOI: 10.1016/j.canlet.2021.10.036

Multiple barriers impede the transformation of evidence-based research into implementation of cervical cancer screening in ASEAN countries. This review is the first of its kind to show the disease burden of cervical cancer, progress till date to implement screening and corresponding challenges, and propose tailored solutions to promote cervical cancer prevention in ASEAN. In 2020, approximately 69 000 cervical cancer cases and 38 000 deaths happened in ASEAN, and more than 44% and 63% increases on new cases and deaths are expected in 2040. Only four countries have initiated population-based cervical cancer screening programs, but the participation rate is less than 50% in some countries and even lower than 10% in Myanmar and Indonesia. Inequity and unavailability in service delivery, lack of knowledge and awareness, limited follow-up and treatment capacity, and funding sustainability affect successful scale-up of cervical cancer screening most in ASEAN. Implementing HPV detection-based primary screening, appropriate management of screen-positives, enhancing health education, integrating health services can accelerate reduction of cervical cancer burden in ASEAN. Achieving high screening coverage and high treatment compliance will help ASEAN countries remain aligned to cervical cancer elimination strategies.

Matched MeSH terms: Papillomaviridae/pathogenicity
Fulltext Blood meal analysis of Anopheles vectors of simian malaria based on laboratory and field studies

Jeyaprakasam NK, Low VL, Liew JWK, Pramasivan S, Wan-Sulaiman WY, Saeung A, et al.

Sci Rep, 2022 01 10;12(1):354.
PMID: 35013403 DOI: 10.1038/s41598-021-04106-w

Blood feeding and host-seeking behaviors of a mosquito play an imperative role in determining its vectorial capacity in transmitting pathogens. Unfortunately, limited information is available regarding blood feeding behavior of Anopheles species in Malaysia. Collection of resting Anopheles mosquitoes for blood meal analysis poses a great challenge especially for forest dwelling mosquitoes. Therefore, a laboratory-based study was conducted to evaluate the potential use of mosquitoes caught using human landing catch (HLC) for blood meal analysis, and subsequently to document blood feeding behavior of local Anopheles mosquitoes in Peninsular Malaysia. The laboratory-based experiment from this study revealed that mosquitoes caught using HLC had the potential to be used for blood meal analysis. Besides HLC, mosquitoes were also collected using manual aspirator and Mosquito Magnet. Overall, 47.4% of 321 field-caught Anopheles mosquitoes belonging to six species were positive for vertebrate host DNA in their blood meal. The most frequent blood meal source was human (45.9%) followed by wild boar (27.4%), dog (15.3%) and monkey (7.5%). Interestingly, only Anopheles cracens and Anopheles introlatus (Leucosphyrus Group) fed on monkey. This study further confirmed that members of the Leucosphyrus Group are the predominant vectors for knowlesi malaria transmission in Peninsular Malaysia mainly due to their simio-anthropophagic feeding behavior.

Matched MeSH terms: Plasmodium knowlesi/pathogenicity*
Fulltext A systematic review of the epidemiology of Hepatitis E virus infection in South - Eastern Asia

Raji YE, Toung OP, Mohd Taib N, Sekawi ZB

Virulence, 2021 12;12(1):114-129.
PMID: 33372843 DOI: 10.1080/21505594.2020.1865716

Hepatitis E virus (HEV) infection is an emerging zoonotic viral disease, with an increasingly international public health challenge. Despite the concerns that the global disease burden may be underestimated. Therefore, evaluation of the disease epidemiology in South - eastern Asia through a systematic review will assist in unraveling the burden of the disease in the subregion. A priori protocol was prepared for the systematic review and followed by a literature search involving five electronic databases. Identified publications were screened for high quality studies and the elimination of bias and relevant data extracted. A total of 4157 citations were captured, and only 35 were included in the review. A wide range of HEV seroprevalence was recorded from 2% (urban blood donors in Malaysia) to 77.7% (lowland communities in Lao PDR). Sporadic HEV infection and epidemics were also detected in the subregion. Indicating hyperendemicity of the disease in South - eastern Asia.

Matched MeSH terms: Hepatitis E virus/pathogenicity
Virulence properties and pathogenicity of multidrug-resistant Vibrio harveyi associated with luminescent vibriosis in Pacific white shrimp, Penaeus vannamei

Nurhafizah WWI, Lee KL, Laith A AR, Nadirah M, Danish-Daniel M, Zainathan SC, et al.

J Invertebr Pathol, 2021 11;186:107594.
PMID: 33878330 DOI: 10.1016/j.jip.2021.107594

Global high demand for Pacific white shrimp Penaeus vannamei has led to intensified cultivation and a wide range of disease problems, including bacterial diseases due to vibrios. Three presumptive luminescent Vibrio harveyi strains (Vh5, Vh8 and Vh10) were isolated from the hepatopancreas (Vh5) and haemolymph (Vh8 and Vh10) of diseased growout Pacific white shrimp from a farm in Setiu, Terengganu, Malaysia, using Vibrio harveyi agar (VHA) differential medium. All three strains were identified as V. harveyi by biochemical characteristics. 16S rRNA gene-based phylogenetic analyses by neighbour-joining, maximum likelihood and maximum parsimony methods showed all three strains in the V. harveyi cluster. All three strains were β-haemolytic and positive for motility, biofilm formation and extracellular products (caseinase, gelatinase, lipase, DNase, amylase and chitinase). Vh10 was subjected to pathogenicity test in Pacific white shrimp by immersion challenge and determined to have a LC50 of 6.0 × 108 CFU mL-1 after 168 h of exposure. Antibiotic susceptibility tests showed that all strains were resistant to oxytetracycline (OXT30), oleandomycin (OL15), amoxicillin (AML25), ampicillin (AMP10) and colistin sulphate (CT25) but sensitive to doxycycline (DO30), flumequine (UB30), oxolinic acid (OA2), chloramphenicol (C30), florfenicol (FFC30), nitrofurantoin (F5) and fosfomycin (FOS50). Each strain was also resistant to a slightly different combination of eight other antibiotics, with an overall multiple antibiotic resistance (MAR) index of 0.40, suggesting prior history of heavy exposure to the antibiotics. Vh10 infection resulted in pale or discoloured hepatopancreas, empty guts, reddening, necrosis and luminescence of uropods, as well as melanised lesions in tail muscle. Histopathological examination showed necrosis of intertubular connective tissue and tubule, sloughing of epithelial cells in hepatopancreatic tubule, haemocytic infiltration, massive vacuolation and loss of hepatopancreatic tubule structure.

Matched MeSH terms: Vibrio/pathogenicity*
Fulltext Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside

Ayipo YO, Yahaya SN, Alananzeh WA, Babamale HF, Mordi MN

Infect Genet Evol, 2021 Sep;93:104944.
PMID: 34052418 DOI: 10.1016/j.meegid.2021.104944

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (Mpro, PLpro, 3CLpro), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.

Matched MeSH terms: Coronavirus/pathogenicity*; Coronavirus OC43, Human/pathogenicity; Middle East Respiratory Syndrome Coronavirus/pathogenicity
Fulltext Current diagnostic approaches to detect two important betacoronaviruses: Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Chong ZX, Liew WPP, Ong HK, Yong CY, Shit CS, Ho WY, et al.

Pathol Res Pract, 2021 Sep;225:153565.
PMID: 34333398 DOI: 10.1016/j.prp.2021.153565

Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two common betacoronaviruses, which are still causing transmission among the human population worldwide. The major difference between the two coronaviruses is that MERS-CoV is now causing sporadic transmission worldwide, whereas SARS-CoV-2 is causing a pandemic outbreak globally. Currently, different guidelines and reports have highlighted several diagnostic methods and approaches which could be used to screen and confirm MERS-CoV and SARS-CoV-2 infections. These methods include clinical evaluation, laboratory diagnosis (nucleic acid-based test, protein-based test, or viral culture), and radiological diagnosis. With the presence of these different diagnostic approaches, it could cause a dilemma to the clinicians and diagnostic laboratories in selecting the best diagnostic strategies to confirm MERS-CoV and SARS-CoV-2 infections. Therefore, this review aims to provide an up-to-date comparison of the advantages and limitations of different diagnostic approaches in detecting MERS-CoV and SARS-CoV-2 infections. This review could provide insights for clinicians and scientists in detecting MERS-CoV and SARS-CoV-2 infections to help combat the transmission of these coronaviruses.

Matched MeSH terms: Middle East Respiratory Syndrome Coronavirus/pathogenicity*
Fulltext Chemical Profile, Antioxidant Properties and Antimicrobial Activities of Malaysian Heterotrigona itama Bee Bread

Suleiman JB, Mohamed M, Abu Bakar AB, Nna VU, Zakaria Z, Othman ZA, et al.

Molecules, 2021 Aug 15;26(16).
PMID: 34443531 DOI: 10.3390/molecules26164943

The aim of the study was to determine the chemical profile, antioxidant properties and antimicrobial activities of Heterotrigona itama bee bread from Malaysia. The pH, presence of phytochemicals, antioxidant properties, total phenolic content (TPC) and total flavonoid content (TFC), as well as antimicrobial activities, were assessed. Results revealed a decrease in the pH of bee bread water extract (BBW) relative to bee bread ethanolic extract (BBE) and bee bread hot water extract (BBH). Further, alkaloids, flavonoids, phenols, tannins, saponins, terpenoids, resins, glycosides and xanthoproteins were detected in BBW, BBH and BBE. Also, significant decreases in TPC, TFC, DPPH activity and FRAP were detected in BBW relative to BBH and BBE. We detected phenolic acids such as gallic acid, caffeic acid, trans-ferulic acid, trans 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, and flavonoids such as quercetin, kaempferol, apigenin and mangiferin in BBE using high-performance liquid chromatography analysis. The strongest antimicrobial activity was observed in Klebsilla pneumonia (MIC50 1.914 µg/mL), followed by E. coli (MIC50 1.923 µg/mL), Shigella (MIC50 1.813 µg/mL) and Salmonella typhi (MIC50 1.617 µg/mL). Bee bread samples possess antioxidant and antimicrobial properties. Bee bread contains phenolic acids and flavonoids, and could be beneficial in the management and treatment of metabolic diseases.

Matched MeSH terms: Escherichia coli/pathogenicity; Salmonella typhi/pathogenicity; Shigella/pathogenicity
Fulltext Viruses join the circular RNA world

Tan KE, Lim YY

FEBS J, 2021 08;288(15):4488-4502.
PMID: 33236482 DOI: 10.1111/febs.15639

Circular RNAs (circRNAs) are a recently discovered class of noncoding RNAs found in many species across the eukaryotic kingdom. These intriguing RNA species are formed through a unique mechanism that is known as back splicing in which the 5' and 3' termini are covalently joined. Recent research has revealed that viruses also encode a repertoire of circRNAs. Some of these viral circRNAs are abundantly expressed and are reported to play a role in disease pathogenesis. A growing number of studies also indicate that host circRNAs are involved in immune responses against virus infections with either an antiviral or proviral role. In this review, we briefly introduce circRNA, its biogenesis, and mechanism of action. We go on to summarize the latest research on the expression, regulation, and functions of viral and host-encoded circRNAs during the host-virus interaction, with the aim of highlighting the potential of viral and host circRNAs as a suitable target for diagnostic biomarker development and therapeutic treatment of viral-associated diseases. We conclude by discussing the current limitations in knowledge and significance of elucidating the roles of circRNAs in host-virus interactions, as well as future directions for this emerging field.

Matched MeSH terms: Viruses/pathogenicity
Fulltext Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape

Bruce JP, To KF, Lui VWY, Chung GTY, Chan YY, Tsang CM, et al.

Nat Commun, 2021 07 07;12(1):4193.
PMID: 34234122 DOI: 10.1038/s41467-021-24348-6

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.

Matched MeSH terms: Herpesvirus 4, Human/pathogenicity
Fulltext A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L

Asghar A, Tan YC, Zahoor M, Zainal Abidin SA, Yow YY, Khan E, et al.

Sci Rep, 2021 Jul 05;11(1):13859.
PMID: 34226594 DOI: 10.1038/s41598-021-92622-0

The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.

Matched MeSH terms: Bacillus subtilis/pathogenicity; Klebsiella pneumoniae/pathogenicity; Pseudomonas aeruginosa/pathogenicity; Salmonella enterica/pathogenicity; Methicillin-Resistant Staphylococcus aureus/pathogenicity
An overview of Acinetobacter baumannii pathogenesis: Motility, adherence and biofilm formation

Mea HJ, Yong PVC, Wong EH

Microbiol Res, 2021 Jun;247:126722.
PMID: 33618061 DOI: 10.1016/j.micres.2021.126722

The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.

Matched MeSH terms: Acinetobacter baumannii/pathogenicity*
Proteasomal degradation of p130 facilitate cell cycle deregulation and impairment of cellular differentiation in high-risk Human Papillomavirus 16 and 18 E7 transfected cells

Gandhi S, Nor Rashid N, Mohamad Razif MF, Othman S

Mol Biol Rep, 2021 Jun;48(6):5121-5133.
PMID: 34169395 DOI: 10.1007/s11033-021-06509-4

The High-Risk Human Papillomaviruses (HR-HPVs) 16 and 18 are known to cause cervical cancer, which is primarily attributed to E6 and E7 oncoproteins. In addition, recent studies have focused on the vital role of the p130 pocket protein as an oncosuppressor to limit the expression of E2F transcription factors required for cell cycle progression. In view of this, the current study was conducted to investigate the mechanism by which transfection with HPV16/18 E7 leads to the deregulation of the host cell cycle, altering the localisation of p130, and expression of differentiation genes in Human Keratinocytes (HaCaT) cells. Co-immunoprecipitation, Western blot analysis, immunofluorescence microscopy, flow cytometry, quantitative-Polymerase Chain Reaction (qPCR), and the inhibition of p130 by MG132 inhibitor were employed to investigate the loss of p130 and its disruption in HPV 16/18 E7-transfected HaCaT cells. The HPV16- and HPV18-transformed cells, known as CaSki and HeLa, respectively, were also used to complement the ectopic expressions of E7 in HaCaT cells. Normal keratinocytes displayed higher level of p130 expression than HPV-transformed cells. In addition, the immunofluorescence analysis revealed that both HPV 16/18 E7-transfected HaCaT and HPV-transformed cells exhibited higher level of cytoplasmic p130 compared to nuclear p130. A significant increase in the number of S/G2 phase cells in HPV-transformed cells was also recorded since E7 has been shown to stimulate proliferation through the deactivation of Retinoblastoma Protein (pRB)-dependent G1/S checkpoint. Furthermore, the findings recorded the down-regulation of keratinocyte differentiation markers, namely p130, keratin10, and involucrin. The proteasomal degradation of the exported p130 confirmed the cellular localisation pattern of p130, which was commonly observed in cancerous cells. The findings provide strong evidence that the localisation of nuclear p130 nuclear was disrupted by HPV16/18 E7 led to the deregulation of the cell cycle and the impairment of cellular differentiation ultimately lead to cellular transformation.

Matched MeSH terms: Human papillomavirus 18/pathogenicity; Human papillomavirus 16/pathogenicity; Alphapapillomavirus/pathogenicity
Fulltext Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India

Das S, Kar A, Manna S, Mandal S, Mandal S, Das S, et al.

Sci Rep, 2021 05 11;11(1):9946.
PMID: 33976269 DOI: 10.1038/s41598-021-89295-0

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P

Matched MeSH terms: Plasmodium falciparum/pathogenicity
Human tuberculosis and Mycobacterium tuberculosis complex: A review on genetic diversity, pathogenesis and omics approaches in host biomarkers discovery

Kanabalan RD, Lee LJ, Lee TY, Chong PP, Hassan L, Ismail R, et al.

Microbiol Res, 2021 May;246:126674.
PMID: 33549960 DOI: 10.1016/j.micres.2020.126674

Mycobacterium tuberculosis complex (MTBC) refers to a group of mycobacteria encompassing nine members of closely related species that causes tuberculosis in animals and humans. Among the nine members, Mycobacterium tuberculosis (M. tuberculosis) remains the main causative agent for human tuberculosis that results in high mortality and morbidity globally. In general, MTBC species are low in diversity but exhibit distinctive biological differences and phenotypes among different MTBC lineages. MTBC species are likely to have evolved from a common ancestor through insertions/deletions processes resulting in species speciation with different degrees of pathogenicity. The pathogenesis of human tuberculosis is complex and remains poorly understood. It involves multi-interactions or evolutionary co-options between host factors and bacterial determinants for survival of the MTBC. Granuloma formation as a protection or survival mechanism in hosts by MTBC remains controversial. Additionally, MTBC species are capable of modulating host immune response and have adopted several mechanisms to evade from host immune attack in order to survive in humans. On the other hand, current diagnostic tools for human tuberculosis are inadequate and have several shortcomings. Numerous studies have suggested the potential of host biomarkers in early diagnosis of tuberculosis, in disease differentiation and in treatment monitoring. "Multi-omics" approaches provide holistic views to dissect the association of MTBC species with humans and offer great advantages in host biomarkers discovery. Thus, in this review, we seek to understand how the genetic variations in MTBC lead to species speciation with different pathogenicity. Furthermore, we also discuss how the host and bacterial players contribute to the pathogenesis of human tuberculosis. Lastly, we provide an overview of the journey of "omics" approaches in host biomarkers discovery in human tuberculosis and provide some interesting insights on the challenges and directions of "omics" approaches in host biomarkers innovation and clinical implementation.

Matched MeSH terms: Mycobacterium tuberculosis/pathogenicity*
Quorum sensing: a new prospect for the management of antimicrobial-resistant infectious diseases

Haque M, Islam S, Sheikh MA, Dhingra S, Uwambaye P, Labricciosa FM, et al.

Expert Rev Anti Infect Ther, 2021 05;19(5):571-586.
PMID: 33131352 DOI: 10.1080/14787210.2021.1843427

INTRODUCTION: Quorum-sensing (QS) is a microbial cell-to-cell communication system that utilizes small signaling molecules to mediates interactions between cross-kingdom microorganisms, including Gram-positive and -negative microbes. QS molecules include N-acyl-homoserine-lactones (AHLs), furanosyl borate, hydroxyl-palmitic acid methylester, and methyl-dodecanoic acid. These signaling molecules maintain the symbiotic relationship between a host and the healthy microbial flora and also control various microbial virulence factors. This manuscript has been developed based on published scientific papers.
AREAS COVERED: Furanones, glycosylated chemicals, heavy metals, and nanomaterials are considered QS inhibitors (QSIs) and are therefore capable of inhibiting the microbial QS system. QSIs are currently being considered as antimicrobial therapeutic options. Currently, the low speed at which new antimicrobial agents are being developed impairs the treatment of drug-resistant infections. Therefore, QSIs are currently being studied as potential interventions targeting QS-signaling molecules and quorum quenching (QQ) enzymes to reduce microbial virulence.
EXPERT OPINION: QSIs represent a novel opportunity to combat antimicrobial resistance (AMR). However, no clinical trials have been conducted thus far assessing their efficacy. With the recent advancements in technology and the development of well-designed clinical trials aimed at targeting various components of the, QS system, these agents will undoubtedly provide a useful alternative to treat infectious diseases.

Matched MeSH terms: Bacteria/pathogenicity
Fulltext Enhanced Pharmaceutically Active Compounds Productivity from Streptomyces SUK 25: Optimization, Characterization, Mechanism and Techno-Economic Analysis

Al-Shaibani MM, Radin Mohamed RMS, Zin NM, Al-Gheethi A, Al-Sahari M, El Enshasy HA

Molecules, 2021 Apr 25;26(9).
PMID: 33923072 DOI: 10.3390/molecules26092510

The present research aimed to enhance the pharmaceutically active compounds' (PhACs') productivity from Streptomyces SUK 25 in submerged fermentation using response surface methodology (RSM) as a tool for optimization. Besides, the characteristics and mechanism of PhACs against methicillin-resistant Staphylococcus aureus were determined. Further, the techno-economic analysis of PhACs production was estimated. The independent factors include the following: incubation time, pH, temperature, shaker rotation speed, the concentration of glucose, mannitol, and asparagine, although the responses were the dry weight of crude extracts, minimum inhibitory concentration, and inhibition zone and were determined by RSM. The PhACs were characterized using GC-MS and FTIR, while the mechanism of action was determined using gene ontology extracted from DNA microarray data. The results revealed that the best operating parameters for the dry mass crude extracts production were 8.20 mg/L, the minimum inhibitory concentrations (MIC) value was 8.00 µg/mL, and an inhibition zone of 17.60 mm was determined after 12 days, pH 7, temperature 28 °C, shaker rotation speed 120 rpm, 1 g glucose /L, 3 g mannitol/L, and 0.5 g asparagine/L with R2 coefficient value of 0.70. The GC-MS and FTIR spectra confirmed the presence of 21 PhACs, and several functional groups were detected. The gene ontology revealed that 485 genes were upregulated and nine genes were downregulated. The specific and annual operation cost of the production of PhACs was U.S. Dollar (U.S.D) 48.61 per 100 mg compared to U.S.D 164.3/100 mg of the market price, indicating that it is economically cheaper than that at the market price.

Matched MeSH terms: Methicillin-Resistant Staphylococcus aureus/pathogenicity
Fulltext Expression of Ascaris lumbricoides putative virulence-associated genes when infecting a human host

Mohd-Shaharuddin N, Lim YAL, Ngui R, Nathan S

Parasit Vectors, 2021 Mar 23;14(1):176.
PMID: 33757548 DOI: 10.1186/s13071-021-04680-y

BACKGROUND: Ascaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally. It is suggested that helminths are capable of evading and manipulating the host immune system through the release of a spectrum of worm proteins which underpins their long-term survival in the host. We hypothesise that the worm overexpresses these proteins when infecting adults compared to children to cirvumvent the more robust defence mechanisms of adults. However, little is known about the parasite's genes and encoded proteins involved during A. lumbricoides infection. Hence, this study was conducted to assess the expression profile of putative virulence-associated genes during an active infection of adults and children.
METHODS: In this study, quantitative PCR was performed to evaluate the expression profile of putative virulence-associated genes in A. lumbricoides isolated from infected children and adults. The study was initiated by collecting adult worms expelled from adults and children following anthelminthic treatment. High-quality RNA was successfully extracted from each of six adult worms expelled by three adults and three children, respectively. Eleven putative homologues of helminth virulence-associated genes reported in previous studies were selected, primers were designed and specific amplicons of A. lumbricoides genes were noted. The expression profiles of these putative virulence-associated genes in A. lumbricoides from infected adults were compared to those in A. lumbricoides from infected children.
RESULTS: The putative virulence-associated genes VENOM, CADHERIN and PEBP were significantly upregulated at 166-fold, 13-fold and fivefold, respectively, in adults compared to children. Conversely, the transcription of ABA-1 (fourfold), CATH-L (threefold) and INTEGRIN (twofold) was significantly suppressed in A. lumbricoides from infected adults.
CONCLUSIONS: On the basis of the expression profile of the putative virulence-associated genes, we propose that the encoded proteins have potential roles in evasion mechanisms, which could guide the development of therapeutic interventions.

Matched MeSH terms: Ascaris lumbricoides/pathogenicity*
Fulltext Spatial and Temporal Patterns of Plasmodium knowlesi Malaria in Sarawak from 2008 to 2017

Ooi CH, Phang WK, Kent Liew JW, Lau YL

Am J Trop Med Hyg, 2021 Mar 22;104(5):1814-1819.
PMID: 33755585 DOI: 10.4269/ajtmh.20-1304

Zoonotic knowlesi malaria has replaced human malaria as the most prevalent malaria disease in Malaysia. The persistence of knowlesi malaria in high-risk transmission areas or hotspots can be discouraging to existing malaria elimination efforts. In this study, retrospective data of laboratory-confirmed knowlesi malaria cases were obtained from the Sarawak Health Department to investigate the spatiotemporal patterns and clustering of knowlesi malaria in the state of Sarawak from 2008 to 2017. Purely spatial, purely temporal, and spatiotemporal analyses were performed using SaTScan software to define clustering of knowlesi malaria incidence. Purely spatial and spatiotemporal analyses indicated most likely clusters of knowlesi malaria in the northern region of Sarawak, along the Sarawak-Kalimantan border, and the inner central region of Sarawak between 2008 and 2017. Temporal cluster was detected between September 2016 and December 2017. This study provides evidence of the existence of statistically significant Plasmodium knowlesi malaria clusters in Sarawak, Malaysia. The analysis approach applied in this study showed potential in establishing surveillance and risk management system for knowlesi malaria control as Malaysia approaches human malaria elimination.

Matched MeSH terms: Plasmodium knowlesi/pathogenicity*
Fulltext Alkyl-Resorcinol Derivatives as Inhibitors of GDP-Mannose Pyrophosphorylase with Antileishmanial Activities

Levaique H, Pamlard O, Apel C, Bignon J, Arriola M, Kuhner R, et al.

Molecules, 2021 Mar 11;26(6).
PMID: 33799883 DOI: 10.3390/molecules26061551

Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania found in tropical and sub-tropical areas, affecting 12 million people around the world. Only few treatments are available against this disease and all of them present issues of toxicity and/or resistance. In this context, the development of new antileishmanial drugs specifically directed against a therapeutic target appears to be a promising strategy. The GDP-Mannose Pyrophosphorylase (GDP-MP) has been previously shown to be an attractive therapeutic target in Leishmania. In this study, a chemical library of 5000 compounds was screened on both L. infantum (LiGDP-MP) and human (hGDP-MP) GDP-MPs. From this screening, oncostemonol D was found to be active on both GDP-MPs at the micromolar level. Ten alkyl-resorcinol derivatives, of which oncostemonols E and J (2 and 3) were described for the first time from nature, were then evaluated on both enzymes as well as on L. infantum axenic and intramacrophage amastigotes. From this evaluation, compounds 1 and 3 inhibited both GDP-MPs at the micromolar level, and compound 9 displayed a three-times lower IC50 on LiGDP-MP, at 11 µM, than on hGDP-MP. As they displayed mild activities on the parasite, these compounds need to be further pharmacomodulated in order to improve their affinity and specificity to the target as well as their antileishmanial activity.

Matched MeSH terms: Leishmania/pathogenicity
Fulltext Lactobacillus plantarum strain HT-W104-B1: potential bacterium isolated from Malaysian fermented foods for control of the dermatophyte Trichophyton rubrum

Danial AM, Medina A, Magan N

World J Microbiol Biotechnol, 2021 Feb 24;37(4):57.
PMID: 33625606 DOI: 10.1007/s11274-021-03020-7

The objective was to screen and evaluate the anti-fungal activity of lactic acid bacteria (LABs) isolated from Malaysian fermented foods against two Trichophyton species. A total of 66 LAB strains were screened using dual culture assays. This showed that four LAB strains were very effective in inhibiting growth of T. rubrum but not T. interdigitale. More detailed studies with Lactobacillus plantarum strain HT-W104-B1 showed that the supernatant was mainly responsible for inhibiting the growth of T. rubrum. The minimum inhibitory concentration (MIC), inhibitory concentration, the 50% growth inhibition (IC50) and minimum fungicide concentration (MFC) were 20 mg/mL, 14 mg/mL and 30 mg/mL, respectively. A total of six metabolites were found in the supernatant, with the two major metabolites being L-lactic acid (19.1 mg/g cell dry weight (CDW)) and acetic acid (2.2 mg/g CDW). A comparative study on keratin agar media showed that the natural mixture in the supernatants predominantly contained L-lactic and acetic acid, and this significantly controlled the growth of T. rubrum. The pure two individual compounds were less effective. Potential exists for application of the natural mixture of compounds for the treatment of skin infection by T. rubrum.

Matched MeSH terms: Trichophyton/pathogenicity

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