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Fulltext Facing the challenges of multidrug-resistant Acinetobacter baumannii: progress and prospects in the vaccine development

Mat Rahim N, Lee H, Strych U, AbuBakar S

Hum Vaccin Immunother, 2021 10 03;17(10):3784-3794.
PMID: 34106809 DOI: 10.1080/21645515.2021.1927412

In 2017, the World Health Organization (WHO) named A. baumannii as one of the three antibiotic-resistant bacterial species on its list of global priority pathogens in dire need of novel and effective treatment. With only polymyxin and tigecycline antibiotics left as last-resort treatments, the need for novel alternative approaches to the control of this bacterium becomes imperative. Vaccines against numerous bacteria have had impressive records in reducing the burden of the respective diseases and addressing antimicrobial resistance; as in the case of Haemophilus influenzae type b . A similar approach could be appropriate for A. baumannii. Toward this end, several potentially protective antigens against A. baumannii were identified and evaluated as vaccine antigen candidates. A licensed vaccine for the bacteria, however, is still not in sight. Here we explore and discuss challenges in vaccine development against A. baumannii and the promising approaches for improving the vaccine development process.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Impact of the Epithelial Lining Fluid Milieu on Amikacin Pharmacodynamics Against Pseudomonas aeruginosa

Heffernan AJ, Sime FB, Lim SMS, Naicker S, Andrews KT, Ellwood D, et al.

Drugs R D, 2021 Jun;21(2):203-215.
PMID: 33797739 DOI: 10.1007/s40268-021-00344-5

BACKGROUND: Even though nebulised administration of amikacin can achieve high epithelial lining fluid concentrations, this has not translated into improved patient outcomes in clinical trials. One possible reason is that the cellular and chemical composition of the epithelial lining fluid may inhibit amikacin-mediated bacterial killing.
OBJECTIVE: The objective of this study was to identify whether the epithelial lining fluid components inhibit amikacin-mediated bacterial killing.
METHODS: Two amikacin-susceptible (minimum inhibitory concentrations of 2 and 8 mg/L) Pseudomonas aeruginosa isolates were exposed in vitro to amikacin concentrations up to 976 mg/L in the presence of an acidic pH, mucin and/or surfactant as a means of simulating the epithelial lining fluid, the site of bacterial infection in pneumonia. Pharmacodynamic modelling was used to describe associations between amikacin concentrations, bacterial killing and emergence of resistance.
RESULTS: In the presence of broth alone, there was rapid and extensive (> 6 - log10) bacterial killing, with emergence of resistance identified in amikacin concentrations < 976 mg/L. In contrast, the rate and extent of bacterial killing was reduced (≤ 5 - log10) when exposed to an acidic pH and mucin. Surfactant did not appreciably impact the bacterial killing or resistance emergence when compared with broth alone for either isolate. The combination of mucin and an acidic pH further reduced the rate of bacterial killing, with the maximal bacterial killing occurring 24 h following initial exposure compared with approximately 4-8 h for either mucin or an acidic pH alone.
CONCLUSIONS: Our findings indicate that simulating the epithelial lining fluid antagonises amikacin-mediated killing of P. aeruginosa, even at the high concentrations achieved following nebulised administration.

Matched MeSH terms: Microbial Sensitivity Tests
Morphinan Alkaloids from the Leaves of Alphonsea cylindrica and Their Antibacterial Properties

Cho KH, Tan SP, Tan HY, Liew SY, Nafiah MA

Planta Med, 2023 Jan;89(1):79-85.
PMID: 35288885 DOI: 10.1055/a-1797-0548

A phytochemical study has been carried out on CH2Cl2 extract of Alphonsea cylindrica leaves, resulting in the isolation of three new morphinan alkaloids. They are kinomenine (1: ), N-methylkinomenine (2: ), and hydroxymethylkinomenine (3: ). The structures of these compounds were elucidated by extensive spectroscopic analysis (1D and 2D NMR, IR, UV, HRESIMS) and comparison with the data reported in literature for similar alkaloids. Kinomenine (1: ) and N-methylkinomenine (2: ) showed weak inhibition against S. aureus (MIC values of 1: and 2: = 500 µg/mL; pIC50 values in 95% C. I. of: 1: = 2.9 to 3.0; 2: = 2.9 to 3.1), while kinomenine (1: ) also showed weak inhibition against E. coli (MIC values of 1: = 500 µg/mL; pIC50 value in 95% C. I. of: 1: = 2.9) by broth microdilution method. The results obtained can be used as future referencefor the discovery of morphinans and the potential of A. cylindrica as an antibacterial source.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext In Vitro Influence of ZnO, CrZnO, RuZnO, and BaZnO Nanomaterials on Bacterial Growth

Abdallah EM, Modwi A, Al-Mijalli SH, Mohammed AE, Idriss H, Omar AS, et al.

Molecules, 2022 Nov 28;27(23).
PMID: 36500402 DOI: 10.3390/molecules27238309

In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria's growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.

Matched MeSH terms: Microbial Sensitivity Tests
Lactoferrin modulates the biofilm formation and bap gene expression of methicillin-resistant Staphylococcus epidermidis

Khanum R, Chung PY, Clarke SC, Chin BY

Can J Microbiol, 2023 Feb 01;69(2):117-122.
PMID: 36265186 DOI: 10.1139/cjm-2022-0135

Lactoferrin is an innate glycoprotein with broad antibacterial and antibiofilm properties. The autonomous antibiofilm activity of lactoferrin against Gram-positive bacteria is postulated to involve the cell wall and biofilm components. Thus, the prevention of biomass formation and eradication of preformed biofilms by lactoferrin was investigated using a methicillin-resistant Staphylococcus epidermidis (MRSE) strain. Additionally, the ability of lactoferrin to modulate the expression of the biofilm-associated protein gene (bap) was studied. The bap gene regulates the production of biofilm-associated proteins responsible for bacterial adhesion and aggregation. In the in vitro biofilm assays, lactoferrin prevented biofilm formation and eradicated established biofilms for up to 24 and 72 h, respectively. Extensive eradication of MRSE biofilm biomass was accompanied by the significant upregulation of bap gene expression. These data suggest the interaction of lactoferrin with the biofilm components and cell wall of MRSE, including the biofilm-associated protein.

Matched MeSH terms: Microbial Sensitivity Tests
Compressed Hydrogen-Induced Synthesis of Quaternary Trimethyl Chitosan-Silver Nanoparticles with Dual Antibacterial and Antifungal Activities

Alli YA, Ejeromedoghene O, Oladipo A, Adewuyi S, Amolegbe SA, Anuar H, et al.

ACS Appl Bio Mater, 2022 Nov 21;5(11):5240-5254.
PMID: 36270024 DOI: 10.1021/acsabm.2c00670

Quaternary Trimethyl Chitosan (QTMC) and QTMC-Silver Nanoparticles (QTMC-AgNPs) have been synthesized, characterized, and tested as antibacterial agents against Staphylococcus aureus, Escherichia coli, and two plant fungi (Sclerotium rolfsil and Fusarium oxysporum). The as-prepared water-soluble QTMC was in situ reacted with silver nitrate in the presence of clean compressed hydrogen gas (3 bar) as a reducing agent to produce QTMC-AgNPs. UV-vis, ATR-FTIR, HR-TEM/SEM, XPS, DLS, XRD, and TGA/DTG were employed to assess the optical response, morphology/size, surface chemistry, particle size distribution, crystal nature, and thermal stability of the synthesized QTMC-AgNPs, respectively. The as-prepared QTMC-AgNPs were quasi-spherical in shape with an average particle size of 12.5 nm, as determined by ImageJ software utilizing HR-TEM images and further validated by DLS analysis. The development of crystalline nanoparticles was confirmed by the presence of distinct and consistent lattice fringes with an approximate interplanar d-spacing of 2.04 nm in QTMC-AgNPs. The QTMC-AgNPs exhibited significant antibacterial activity with a clear zone of inhibition of 30 mm and 26 mm around the disks against E. coli and S. aureus, respectively. In addition, QTMC-AgNPs showed highly efficient antifungal activity with 100% and 76.67% growth inhibition against two plant pathogens, S. rolfsii and F. oxysporum, respectively, whereas QTMC revealed no impact. Overall, QTMC-AgNPs showed a promising therapeutic potential and,thus, can be considered for drug design rationale.

Matched MeSH terms: Microbial Sensitivity Tests
Mutations in Genes Encoding 23S rRNA and FadD32 May be Associated with Linezolid Resistance in Mycobacteroides abscessus

Ng HF, Ngeow YF

Microb Drug Resist, 2023 Feb;29(2):41-46.
PMID: 36802272 DOI: 10.1089/mdr.2022.0068

Linezolid is one of the antibiotics used to treat the Mycobacteroides abscessus infection. However, linezolid-resistance mechanisms of this organism are not well understood. The objective of this study was to identify possible linezolid-resistance determinants in M. abscessus through characterization of step-wise mutants selected from a linezolid-susceptible strain, M61 (minimum inhibitory concentration [MIC]: 0.25 mg/L). Whole-genome sequencing and subsequent PCR verification of the resistant second-step mutant, A2a(1) (MIC: >256 mg/L), revealed three mutations in its genome, two of which were found in the 23S rDNA (g2244t and g2788t) and another one was found in a gene encoding the fatty-acid-CoA ligase FadD32 (c880t→H294Y). The 23S rRNA is the molecular target of linezolid and mutations in this gene are likely to contribute to resistance. Furthermore, PCR analysis revealed that the c880t mutation in the fadD32 gene first appeared in the first-step mutant, A2 (MIC: 1 mg/L). Complementation of the wild-type M61 with the pMV261 plasmid carrying the mutant fadD32 gene caused the previously sensitive M61 to develop a reduced susceptibility to linezolid (MIC: 1 mg/L). The findings of this study uncovered hitherto undescribed mechanisms of linezolid resistance in M. abscessus that may be useful for the development of novel anti-infective agents against this multidrug-resistant pathogen.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Serological detection of enterotoxin from food poisoning strains of Staphylococcus aureus isolated in Malaysia

Lim YS, Jegathesan M, Koay AS

Singapore Med J, 1985 Jun;26(3):304-6.
PMID: 4048994

Cultures of Staphylococcus aureus from eight food poisoning incidents in Malaysia were examined for their ability to produce enterotoxins. Five of the eight strains were found to be enterotoxigenic, the enterotoxins detected being A and E (three strains), A and C (one strain), and C (one strain). Penicillinase production was observed in four of the five enterotoxigenic strains; the penicillin·sensitive strain was also found to be coagulase-negative. The bacteriological and epidemiological investigations for confirming staphylococcal food poisoning are presented. The preventive measures to be taken in reducing such outbreaks are emphasized.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Exploring Cefiderocol Resistance Mechanisms in Burkholderia pseudomallei

Hall CM, Somprasong N, Hagen JP, Nottingham R, Sahl JW, Webb JR, et al.

Antimicrob Agents Chemother, 2023 Jun 15;67(6):e0017123.
PMID: 37133377 DOI: 10.1128/aac.00171-23

Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by β-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with in vitro resistance found in a few isolates. Resistance in clinical B. pseudomallei isolates from Australia is caused by a hitherto uncharacterized mechanism. We show that, like in other Gram-negatives, the PiuA outer membrane receptor plays a major role in cefiderocol nonsusceptibility in isolates from Malaysia.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Recent Advances in Pyridine Scaffold: Focus on Chemistry, Synthesis, and Antibacterial Activities

Islam MB, Islam MI, Nath N, Emran TB, Rahman MR, Sharma R, et al.

Biomed Res Int, 2023;2023:9967591.
PMID: 37250749 DOI: 10.1155/2023/9967591

Multidrug-resistant (MDR) pathogens have created a fatal problem for human health and antimicrobial treatment. Among the currently available antibiotics, many are inactive against MDR pathogens. In this context, heterocyclic compounds/drugs play a vital role. Thus, it is very much essential to explore new research to combat the issue. Of the available nitrogen-bearing heterocyclic compounds/drugs, pyridine derivatives are of special interest due to their solubility. Encouragingly, some of the newly synthesized pyridine compounds/drugs are found to inhibit multidrug-resistant S. aureus (MRSA). Pyridine scaffold bearing poor basicity generally improves water solubility in pharmaceutically potential molecules and has led to the discovery of numerous broad-spectrum therapeutic agents. Keeping these in mind, we have reviewed the chemistry, recent synthetic techniques, and bacterial preventative activity of pyridine derivatives since 2015. This will facilitate the development of pyridine-based novel antibiotic/drug design in the near future as a versatile scaffold with limited side effects for the next-generation therapeutics.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext An intriguing approach toward antibacterial activity of green synthesized Rutin-templated mesoporous silica nanoparticles decorated with nanosilver

Abbasi M, Gholizadeh R, Kasaee SR, Vaez A, Chelliapan S, Fadhil Al-Qaim F, et al.

Sci Rep, 2023 Apr 12;13(1):5987.
PMID: 37046068 DOI: 10.1038/s41598-023-33095-1

In recent years, mesoporous silica nanoparticles (MSNs) have been applied in various biomedicine fields like bioimaging, drug delivery, and antibacterial alternatives. MSNs could be manufactured through green synthetic methods as environmentally friendly and sustainable synthesis approaches, to improve physiochemical characteristics for biomedical applications. In the present research, we used Rutin (Ru) extract, a biocompatible flavonoid, as the reducing agent and nonsurfactant template for the green synthesis of Ag-decorated MSNs. Transmission electron microscopy (TEM), zeta-potential, x-ray powder diffraction (XRD), fourier transform infrared (FTIR) spectroscopy analysis, scanning electron microscopy (SEM), brunauer-emmett-teller (BET) analysis, and energy-dispersive system (EDS) spectroscopy were used to evaluate the Ag-decorated MSNs physical characteristics. The antimicrobial properties were evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and also different types of candida. The cytotoxicity test was performed by using the MTT assay. Based on the findings, the significant antimicrobial efficacy of Ru-Ag-decorated MSNs against both gram positive and gram negative bacteria and different types of fungi was detected as well as acceptable safety and low cytotoxicity even at lower concentrations. Our results have given a straightforward and cost-effective method for fabricating biodegradable Ag-decorated MSNs. The applications of these MSNs in the domains of biomedicine appear to be promising.

Matched MeSH terms: Microbial Sensitivity Tests
Computational modelling of potential Zn-sensitive non-β-lactam inhibitors of imipenemase-1 (IMP-1)

Ayipo YO, Ahmad I, Alananzeh W, Lawal A, Patel H, Mordi MN

J Biomol Struct Dyn, 2023 Nov;41(19):10096-10116.
PMID: 36476097 DOI: 10.1080/07391102.2022.2153168

Antibiotic resistance (AR) remains one of the leading global health challenges, mostly implicated in disease-related deaths. The Enterobacteriaceae-producing metallo-β-lactamases (MBLs) are critically involved in AR pathogenesis through Zn-dependent catalytic destruction of β-lactam antibiotics, yet with limited successful clinical inhibitors. The efficacy of relevant broad-spectrum β-lactams including imipenem and meropenem are seriously challenged by their susceptibility to the Zn-dependent carbapenemase hydrolysis, as such, searching for alternatives remains imperative. In this study, computational molecular modelling and virtual screening methods were extensively applied to identify new putative Zn-sensitive broad-spectrum inhibitors of MBLs, specifically imipenemase-1 (IMP-1) from the IBScreen database. Three ligands, STOCK3S-30154, STOCK3S-30418 and STOCK3S-30514 selectively displayed stronger binding interactions with the enzymes compared to reference inhibitors, imipenem and meropenem. For instance, the ligands showed molecular docking scores of -9.450, -8.005 and -10.159 kcal/mol, and MM-GBSA values of -40.404, -31.902 and -33.680 kcal/mol respectively against the IMP-1. Whereas, imipenem and meropenem showed docking scores of -9.038 and -10.875 kcal/mol, and MM-GBSA of -31.184 and -32.330 kcal/mol respectively against the enzyme. The ligands demonstrated good thermodynamic stability and compactness in complexes with IMP-1 throughout the 100 ns molecular dynamics (MD) trajectories. Interestingly, their binding affinities and stabilities were significantly affected in contacts with the remodelled Zn-deficient IMP-1, indicating sensitivity to the carbapenemase active Zn site, however, with non-β-lactam scaffolds, tenable to resist catalytic hydrolysis. They displayed ideal drug-like ADMET properties, thus, representing putative Zn-sensitive non-β-lactam inhibitors of IMP-1 amenable for further experimental studies.

Matched MeSH terms: Microbial Sensitivity Tests
The phenotypes and genotypes associated with biofilm formation among methicillin-susceptible Staphylococcus aureus (MSSA) isolates collected from a tertiary hospital in Terengganu, Malaysia

Jones SU, Chew CH, Yeo CC, Abdullah FH, Othman N, Kee BP, et al.

Int Microbiol, 2023 Nov;26(4):841-849.
PMID: 36805382 DOI: 10.1007/s10123-023-00335-3

Methicillin-susceptible Staphylococcus aureus (MSSA) is an important nosocomial pathogen worldwide. This study aims to investigate the in vitro biofilm-forming ability of clinical MSSA isolated from various sources in the main public tertiary referral hospital in Terengganu, Malaysia and to detect the presence of biofilm-associated and regulatory genes among these isolates. A total of 104 MSSA isolates [pus (n = 75), blood (n = 24), respiratory secretions (n = 2), eye (n = 2), and urine (n = 1)] were investigated for slime production and biofilm formation using Congo red agar and crystal violet microtitre plate, respectively. Fifteen MSSA isolates with varying degrees of biofilm formation were selected for validation via a real-time cell analyser. All isolates were screened for microbial surface components recognising adhesive matrix molecules (MSCRAMM) and accessory gene regulator (agr) using polymerase chain reaction assay. A total of 76.0% (79/104) isolates produced slime layer, while all isolates developed biofilm as follows: 52.8% (55/104) strong biofilm producers, 40.4% (42/104) intermediate biofilm producers, and 6.7% (7/104) weak biofilm producers. A total of 98.1% (102/104) isolates carried at least one of the screened MSCRAMM gene(s) with the eno gene detected at the highest rate (87.5%, 91/104), while the sasG gene was significantly associated with strong biofilm production (p = 0.015). Three agr groups, 1, 2, and 3, were detected among the MSSA isolates with a predominance of agr-3 (32.7%, 34/104). In conclusion, biofilm formation varied greatly among clinical MSSA isolates, and the presence of sasG gene and agr-1 may play important role in initiating MSSA infections via biofilm formation.

Matched MeSH terms: Microbial Sensitivity Tests
Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates

Spruijtenburg B, Ahmad S, Asadzadeh M, Alfouzan W, Al-Obaid I, Mokaddas E, et al.

Mycoses, 2023 Dec;66(12):1079-1086.
PMID: 37712885 DOI: 10.1111/myc.13655

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Genomic and phenotypic characterization of Acinetobacter colistiniresistens isolated from the feces of a healthy member of the community

Muzahid NH, Md Zoqratt MZH, Ten KE, Hussain MH, Su TT, Ayub Q, et al.

Sci Rep, 2023 Aug 03;13(1):12596.
PMID: 37537198 DOI: 10.1038/s41598-023-39642-0

Acinetobacter species are widely known opportunistic pathogens causing severe community and healthcare-associated infections. One such emerging pathogen, Acinetobacter colistiniresistens, is known to exhibit intrinsic resistance to colistin. We investigated the molecular characteristics of A. colistiniresistens strain C-214, isolated from the fecal sample of a healthy community member, as part of a cohort study being conducted in Segamat, Malaysia. Comparison of the whole genome sequence of C-214 with other A. colistiniresistens sequences retrieved from the NCBI database showed 95% sequence identity or more with many of the genome sequences representing that species. Use of the Galleria mellonella killing assay showed that C-214 was pathogenic in this model infection system. The strain C-214 had a colistin and polymyxin B MIC of 32 and 16 mg/L, respectively. Besides, it was resistant to cefotaxime, amikacin, and tetracycline and showed moderate biofilm-producing ability. Different genes associated with virulence or resistance to major classes of antibiotics were detected. We observed mutations in lpxA/C/D in C-214 and other A. colistiniresistens strains as probable causes of colistin resistance, but the biological effects of these mutations require further investigation. This study provides genomic insights into A. colistiniresistens, a potentially pathogenic bacterium isolated from a community member and notes the public health threat it may pose.

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Proof-of-concept for incorporating mechanistic insights from multi-omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae

Hanafin PO, Abdul Rahim N, Sharma R, Cess CG, Finley SD, Bergen PJ, et al.

CPT Pharmacometrics Syst Pharmacol, 2023 Mar;12(3):387-400.
PMID: 36661181 DOI: 10.1002/psp4.12923

Carbapenemase-resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time-kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism-based model (MBM) was developed using time-kill data in S-ADAPT describing PMB-CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax : 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one-compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi-omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi-omics responses via a multi-omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2 = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi-omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.

Matched MeSH terms: Microbial Sensitivity Tests
Dielectrophoresis microbial characterization and isolation of Staphylococcus aureus based on optimum crossover frequency

Rozaini AZA, Abdulhameed A, Deivasigamani R, Nadzreen N, Zin NM, Kayani AA, et al.

Electrophoresis, 2023 Aug;44(15-16):1220-1233.
PMID: 37259263 DOI: 10.1002/elps.202200276

Characterization of antibiotic-resistant bacteria is a significant concern that persists for the rapid classification and analysis of the bacteria. A technology that utilizes the manipulation of antibiotic-resistant bacteria is key to solving the significant threat of these pathogenic bacteria by rapid characterization profile. Dielectrophoresis (DEP) can differentiate between antibiotic-resistant and susceptible bacteria based on their physical structure and polarization properties. In this work, the DEP response of two Gram-positive bacteria, namely, Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-susceptible S. aureus (MSSA), was investigated and simulated. The DEP characterization was experimentally observed on the bacteria influenced by oxacillin and vancomycin antibiotics. MSSA control without antibiotics has crossover frequencies ( f x 0 ${f_{x0}}$ ) from 6 to 8 MHz, whereas MRSA control is from 2 to 3 MHz. The f x 0 ${f_{x0}}$ changed when bacteria were exposed to the antibiotic. As for MSSA, the f x 0 ${f_{x0}}$ decreased to 3.35 MHz compared to f x 0 ${f_{x0}}$ MSSA control without antibiotics, MRSA, f x 0 ${f_{x0}}$ increased to 7 MHz when compared to MRSA control. The changes in the DEP response of MSSA and MRSA with and without antibiotics were theoretically proven using MyDEP and COMSOL simulation and experimentally based on the modification to the bacteria cell walls. Thus, the DEP response can be employed as a label-free detectable method to sense and differentiate between resistant and susceptible strains with different antibiotic profiles. The developed method can be implemented on a single platform to analyze and identify bacteria for rapid, scalable, and accurate characterization.

Matched MeSH terms: Microbial Sensitivity Tests
Green synthesis, characterisation and antibacterial activities of Strobilanthes crispus-mediated silver nanoparticles (SC-AGNPS) against selected bacteria

Mohamad Hanafiah R, Abd Ghafar SA, Lim V, Musa SNA, Yakop F, Hairil Anuar AH

Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):549-559.
PMID: 37847252 DOI: 10.1080/21691401.2023.2268167

This study aims to characterize and determine the antibacterial activities of synthesized Strobilanthes crispus-mediated AgNPs (SC-AgNPs) against Streptococcus mutans, Escherichia coli and Pseudomonas aeruginosa. S. crispus water extract acts as a reducing and capping agent in the synthesis of AgNPs. The synthesized AgNPs were characterized by using UV-Vis spectrophotometer, dynamic light scattering (DLS), field emission scanning electron microscope (FESEM), X-ray diffractometer (XRD) and Fourier transform infra-red (FTIR). FESEM images showed a rough surface with a spherical shape. The average size distribution of 75.25 nm with a polydispersity index (PDI) of 0.373. XRD analysis matched the face-centred cubic structure of silver. FTIR analysis revealed a shifted peak from 1404.99 to 1345.00 cm-1. MIC and MBC values of SC-AgNPs were 1.25 mg/mL and 2.5 mg/mL against E. coli, P. aeruginosa and S. mutans, respectively. Time-kill assay showed that SC-AgNPs significantly reduced bacterial growth as compared to non-treated bacteria. Morphologies of bacteria treated with SC-AgNPs were shrunk, lysed, irregular and smaller as compared to control. SC-AgNPs significantly disrupted the gene expression of eae A, gtf B and Pel A (p

Matched MeSH terms: Microbial Sensitivity Tests
Fulltext Development and Evaluation of Topical Zinc Oxide Nanogels Formulation Using Dendrobium anosmum and Its Effect on Acne Vulgaris

Tan YY, Wong LS, Nyam KL, Wittayanarakul K, Zawawi NA, Rajendran K, et al.

Molecules, 2023 Sep 22;28(19).
PMID: 37836592 DOI: 10.3390/molecules28196749

Zinc oxide nanoparticles have high levels of biocompatibility, a low impact on environmental contamination, and suitable to be used as an ingredient for environmentally friendly skincare products. In this study, biogenically synthesized zinc oxide nanoparticles using Dendrobium anosum are used as a reducing and capping agent for topical anti-acne nanogels, and the antimicrobial effect of the nanogel is assessed on Cutibacterium acne and Staphylococcus aureus. Dendrobium anosmum leaf extract was examined for the presence of secondary metabolites and its total amount of phenolic and flavonoid content was determined. Both the biogenically and chemogenic-synthesized zinc oxide nanoparticles were compared using UV-Visible spectrophotometer, FE-SEM, XRD, and FTIR. To produce the topical nanogel, the biogenic and chemogenic zinc oxide nanoparticles were mixed with a carbomer and hydroxypropyl-methyl cellulose (HPMC) polymer. The mixtures were then tested for physical and chemical characteristics. To assess their anti-acne effectiveness, the mixtures were tested against C. acne and S. aureus. The biogenic zinc oxide nanoparticles have particle sizes of 20 nm and a high-phase purity. In comparison to chemogenic nanoparticles, the hydrogels with biogenically synthesized nanoparticles was more effective against Gram-positive bacteria. Through this study, the hybrid nanogels was proven to be effective against the microbes that cause acne and to be potentially used as a green product against skin infections.

Matched MeSH terms: Microbial Sensitivity Tests
Bacteria associated with wild mud crab (Scylla serrata) from Setiu Wetland, Malaysia with emphasis on antibiotic resistances

Najiah M, Nadirah M, Sakri I, Shaharom-Harrison F

Pak J Biol Sci, 2010 Mar 15;13(6):293-7.
PMID: 20506717

A study was carried out to investigate the presence of bacteria flora in wild mud crab (Scylla serrata) from Setiu Wetland as well as their antibiotic resistances. A total of 91 bacterial isolates consisting of 12 bacterial species were successfully isolated from mud crab. Oxolinic acid was found to be effective against all the bacterial isolates whilst the highest percentage of antibiotic resistance was shown by lincomycin (94.5%) followed by ampicillin (90.1%), amoxicillin (86.8%) and oleandomycin (78.0%). The study is very useful to evaluate the safety of mud crab for human consumption based on wild mud crab-associated bacteria as well as their antibiotic resistances.

Matched MeSH terms: Microbial Sensitivity Tests

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