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  1. Fulltext MgrB Mutations and Altered Cell Permeability in Colistin Resistance in Klebsiella pneumoniae
    Yap PS, Cheng WH, Chang SK, Lim SE, Lai KS
    Cells, 2022 Sep 26;11(19).
    PMID: 36230959 DOI: 10.3390/cells11192995
    There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  2. Fulltext Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil
    Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, Akseer R, et al.
    PLoS One, 2019;14(4):e0214326.
    PMID: 30939149 DOI: 10.1371/journal.pone.0214326
    Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  3. Metabonomics reveals an alleviation of fitness cost in resistant E. coli competing against susceptible E. coli at sub-MIC doxycycline
    Wen X, Cao J, Mi J, Huang J, Liang J, Wang Y, et al.
    J Hazard Mater, 2021 03 05;405:124215.
    PMID: 33109407 DOI: 10.1016/j.jhazmat.2020.124215
    High concentrations of antibiotics may induce bacterial resistance mutations and further lead to fitness costs by reducing growth of resistant bacteria. However, antibiotic concentrations faced by bacteria are usually low in common environments, which leads to questions about how resistant bacteria with fitness costs regulate metabolism to coexist or compete with susceptible bacteria during sublethal challenge. Our study revealed that a low proportion (< 15%) of resistant bacteria coexisted with susceptible bacteria due to the fitness cost without doxycycline. However, the cost for the resistant strain decreased at a doxycycline concentration of 1 mg/L and even disappeared when the doxycycline concentration was 2 mg/L. Metabonomics analysis revealed that bypass carbon metabolism and biosynthesis of secondary metabolites were the primary metabolic pathways enriching various upregulated metabolites in resistant bacteria without doxycycline. Moreover, the alleviation of fitness cost for resistant bacteria competed with susceptible bacteria at 1 mg/L doxycycline was correlated with the downregulation of the biomarkers pyruvate and pilocarpine. Our study offered new insight into the metabolic mechanisms by which the fitness cost of resistant mutants was reduced at doxycycline concentrations as low as 1 mg/L and identified various potential metabolites to limit the spread of antimicrobial resistance in the environment.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  4. Occurrence and contamination profiles of antibiotic resistance genes from swine manure to receiving environments in Guangdong Province southern China
    Wen X, Mi J, Wang Y, Ma B, Zou Y, Liao X, et al.
    Ecotoxicol Environ Saf, 2019 May 30;173:96-102.
    PMID: 30769208 DOI: 10.1016/j.ecoenv.2019.02.023
    Livestock farms are commonly regarded as the main sources of antibiotic resistance genes (ARGs), emerging pollutants with potential implications for human health, in the environment. This study investigated the occurrence and contamination profiles of nine ARGs of three types from swine manure to receiving environments (soil and water) in Guangdong Province, southern China. All ARGs occurred in 100% of swine manure samples. Moreover, the absolute concentration of total ARGs varied from 3.01 × 108 to 7.18 × 1014 copies/g, which was significantly higher than that in wastewater and manured soil (p  0.05). However, the number of ARGs (ermB, qnrS, acc(6')-Ib, tetM, tetO and tetQ) decreased but were not eliminated by wastewater treatment components (p 
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  5. Elucidating isoniazid resistance using molecular modeling
    Wahab HA, Choong YS, Ibrahim P, Sadikun A, Scior T
    J Chem Inf Model, 2009 Jan;49(1):97-107.
    PMID: 19067649 DOI: 10.1021/ci8001342
    The continuing rise in tuberculosis incidence and the problem of drug resistance strains have prompted the research on new drug candidates and the mechanism of drug resistance. Molecular docking and molecular dynamics simulation (MD) were performed to study the binding of isoniazid onto the active site of Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) in an attempt to address the mycobacterial resistance against isoniazid. Results show that isonicotinic acyl-NADH (INADH) has an extremely high binding affinity toward the wild type InhA by forming stronger interactions compared to the parent drug (isoniazid) (INH). Due to the increase of hydrophobicity and reduction in the side chain's volume of A94 of mutant type InhA, both INADH and the mutated protein become more mobile. Due to this reason, the molecular interactions of INADH with mutant type are weaker than that observed with the wild type. However, the reduced interaction caused by the fluctuation of INADH and the mutant protein only inflected minor resistance in the mutant strain as inferred from free energy calculation. MD results also showed there exists a water-mediated hydrogen bond between INADH and InhA. However, the bridged water molecule is only present in the INADH-wild type complex, reflecting the putative role of the water molecule in the binding of INADH to the wild type protein. The results support the assumption that the conversion of prodrug isoniazid into its active form INADH is mediated by KatG as a necessary step prior to target binding on InhA. Our findings also contribute to a better understanding of INH resistance in mutant type.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  6. Enterobacteriaceae resistant to third-generation cephalosporins and quinolones in fresh culinary herbs imported from Southeast Asia
    Veldman K, Kant A, Dierikx C, van Essen-Zandbergen A, Wit B, Mevius D
    Int J Food Microbiol, 2014 May 2;177:72-7.
    PMID: 24607424 DOI: 10.1016/j.ijfoodmicro.2014.02.014
    Since multidrug resistant bacteria are frequently reported from Southeast Asia, our study focused on the occurrence of ESBL-producing Enterobacteriaceae in fresh imported herbs from Thailand, Vietnam and Malaysia. Samples were collected from fresh culinary herbs imported from Southeast Asia in which ESBL-suspected isolates were obtained by selective culturing. Analysis included identification by MALDI-TOF mass spectrometry, susceptibility testing, XbaI-PFGE, microarray, PCR and sequencing of specific ESBL genes, PCR based replicon typing (PBRT) of plasmids and Southern blot hybridization. In addition, the quinolone resistance genotype was characterized by screening for plasmid mediated quinolone resistance (PMQR) genes and mutations in the quinolone resistance determining region (QRDR) of gyrA and parC. The study encompassed fifty samples of ten batches of culinary herbs (5 samples per batch) comprising nine different herb variants. The herbs originated from Thailand (Water morning glory, Acacia and Betel leaf), Vietnam (Parsley, Asian pennywort, Houttuynia leaf and Mint) and Malaysia (Holy basil and Parsley). By selective culturing 21 cefotaxime resistant Enterobacteriaceae were retrieved. Array analysis revealed 18 isolates with ESBL genes and one isolate with solely non-ESBL beta-lactamase genes. Mutations in the ampC promoter region were determined in two isolates with PCR and sequencing. The isolates were identified as Klebsiella pneumoniae (n=9), Escherichia coli (n=6), Enterobacter cloacae complex (n=5) and Enterobacter spp. (n=1). All isolates tested were multidrug resistant. Variants of CTX-M enzymes were predominantly found followed by SHV enzymes. PMQR genes (including aac(6')-1b-cr, qnrB and qnrS) were also frequently detected. In almost all cases ESBL and quinolone resistance genes were located on the same plasmid. Imported fresh culinary herbs from Southeast Asia are a potential source for contamination of food with multidrug resistant bacteria. Because these herbs are consumed without appropriate heating, transfer to human bacteria cannot be excluded.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  7. Fulltext Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia
    Subramaniam P, Jabar KA, Kee BP, Chong CW, Nathan AM, de Bruyne J, et al.
    Indian J Med Res, 2018 Aug;148(2):225-231.
    PMID: 30381546 DOI: 10.4103/ijmr.IJMR_1987_16
    Background & objectives: Streptococcus pneumoniae: (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia.

    Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated.

    Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F.

    Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.

    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  8. High prevalence of qacA/B carriage among clinical isolates of meticillin-resistant Staphylococcus aureus in Malaysia
    Shamsudin MN, Alreshidi MA, Hamat RA, Alshrari AS, Atshan SS, Neela V
    J Hosp Infect, 2012 Jul;81(3):206-8.
    PMID: 22633074 DOI: 10.1016/j.jhin.2012.04.015
    The minimum inhibitory concentrations (MICs) of 60 meticillin-resistant Staphylococcus aureus (MRSA) isolates from Malaysia to three antiseptic agents - benzalkonium chloride (BZT), benzethonium chloride (BAC) and chlorhexidine digluconate (CHG) - were determined. All isolates had MICs ranging from 0.5 to 2 mg/L. Antiseptic resistance genes qacA/B and smr were detected in 83.3% and 1.6% of the isolates, respectively. Carriage of qacA/B correlated with reduced susceptibility to CHG and BAC. This is the first report of the prevalence of qacA/B and smr gene carriage in Malaysian MRSA isolates, with a high frequency of qacA/B carriage. The presence of these antiseptic resistance genes and associated reduced susceptibility to antiseptic agents may have clinical implications.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  9. Antibiotic resistance and determination of resistant genes among cockle (Anadara granosa) isolates of Vibrio alginolyticus
    Shahimi S, Elias A, Abd Mutalib S, Salami M, Fauzi F, Mohd Zaini NA, et al.
    Environ Sci Pollut Res Int, 2021 Aug;28(32):44002-44013.
    PMID: 33846919 DOI: 10.1007/s11356-021-13665-4
    A total of 24 strains of Vibrio alginolyticus were isolated from cockles (Anadara granosa) and identified for VibA and gyrB genes. All V. alginolyticus isolates were then tested against nine different antibiotics. In this study, the highest percentage of antibiotic resistance was obtained against penicillin (37.50%), followed by ampicillin, vancomycin (12.50%) and erythromycin (8.33%). All of V. alginolyticus isolates were susceptible against streptomycin, kanamycin, tetracycline, chloramphenicol and sulfamethoxazole. Polymerase chain reaction (PCR) assay has confirmed the presence of four antibiotic resistance genes of penicillin (pbp2a), ampicillin (blaOXA), erythromycin (ermB) and vancomycin (vanB). Out of 24 V. alginolyticus isolates, 2 isolates possessed the tdh-related hemolysin (trh) (strains VA15 and VA16) and none for the thermostable direct hemolysin (tdh) gene. Both strains of the tdh-related hemolysin (trh) were susceptible to all antibiotics tested. The multiple antibiotic resistance (MAR) index ranging between 0.2 and 0.3 with 5 antibiograms (A1-A5) was observed. Combination of enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and antibiotic resistance indicated 18 genome types which showed genetic heterogeneity of those V. alginolyticus isolates. The results demonstrated the presence of V. alginolyticus strain found in cockles can be a potential risk to consumers and can contribute to the deterioration of human health in the study area. Thus, it is essential for local authority to provide the preventive measures in ensuring the cockles are safe for consumption.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  10. Fulltext Do the clonally different Escherichia coli isolates causing different infections in a HIV positive patient affect the selection of antibiotics for their treatment?
    Rameshkumar MR, Arunagirinathan N, Swathirajan CR, Vignesh R, Balakrishnan P, Solomon SS
    Indian J Med Res, 2018 09;148(3):341-344.
    PMID: 30425226 DOI: 10.4103/ijmr.IJMR_730_17
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  11. Fulltext Next generation sequencing reveals the antibiotic resistant variants in the genome of Pseudomonas aeruginosa
    Ramanathan B, Jindal HM, Le CF, Gudimella R, Anwar A, Razali R, et al.
    PLoS One, 2017;12(8):e0182524.
    PMID: 28797043 DOI: 10.1371/journal.pone.0182524
    Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation. These nsSNPs identified in the multi-drug resistant clinical isolates were found to be altering a single amino acid in several antibiotic resistant genes. We found mutations in genes encoding efflux pump systems, cell wall, DNA replication and genes involved in repair mechanism. In addition, nucleotide deletions in the genome and mutations leading to generation of stop codons were also observed in the antibiotic resistant clinical isolates. Next generation sequencing is a powerful tool to compare the whole genomes and analyse the single base pair variations found within the antibiotic resistant genes. We identified specific mutations within antibiotic resistant genes compared to the susceptible strain of the same bacterial species and these findings may provide insights to understand the role of single nucleotide variants in antibiotic resistance.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  12. Modifications in the pmrB gene are the primary mechanism for the development of chromosomally encoded resistance to polymyxins in uropathogenic Escherichia coli
    Phan MD, Nhu NTK, Achard MES, Forde BM, Hong KW, Chong TM, et al.
    J Antimicrob Chemother, 2017 10 01;72(10):2729-2736.
    PMID: 29091192 DOI: 10.1093/jac/dkx204
    Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958.

    Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.

    Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.

    Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli.

    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  13. Fulltext Analysis of PCR-RAPD DNA and antibiotic susceptibility profiles of antrum and corpus isolates of Helicobacter pylori from Malaysian patients
    Norazah A, Rasinah WZ, Zaili Z, Aminuddin A, Ramelah M
    Malays J Pathol, 2009 Jun;31(1):29-34.
    PMID: 19694311 MyJurnal
    This study was conducted to determine whether there was any genetic heterogeneity among Helicobacter pylori strains isolated from the antrum and corpus of the same individual in a Malaysian population and to determine the presence of heterogeneous susceptibility of the isolates by comparing PCR-RAPD and antibiotic profiles. Forty-four H. pylori isolates cultured from the antrum and corpus of 22 patients were analyzed. Antibiotic susceptibility testing was carried out by minimum inhibitory concentration determination, using E-Test method strips. PCR-RAPD was carried out on all the strains and the profiles generated were analysed for cluster analysis. Twenty-nine different PCR-RAPD profiles were observed in the 44 isolates. Fifteen pairs of the isolates from the same patients had the same PCR-RAPD patterns while in 7 pairs, the profiles were different. The strains were clustered into 2 separate clusters at a low coefficient of similarity, where most of the strains were in cluster 1. The degree of similarity was very low among most of the isolates. Most of the patients (16 of 22) were infected with strains that have the same antibiotic susceptibility profiles. Out of these, only 10 pairs shared the same PCR-RAPD and antibiotic profiles. Five pairs of isolates with similar PCR-RAPD profiles differed in their antibiotic profiles due to metronidazole resistance in one of the sites. A large degree of genetic heterogeneity was observed among H. pylori strains circulating among Malaysian patients. An individual patient can be infected with multiple strains and the strains can be antibiotic resistant.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  14. Fulltext High resolution melting analysis for rapid mutation screening in gyrase and Topoisomerase IV genes in quinolone-resistant Salmonella enterica
    Ngoi ST, Thong KL
    Biomed Res Int, 2014;2014:718084.
    PMID: 25371903 DOI: 10.1155/2014/718084
    The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM) assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR) of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (n = 52; S83F, S83Y, S83I, D87G, D87Y, and D87N) and parE (n = 1; M438I). Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC 16 > 256 μg/mL). Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  15. Molecular characterization showed limited genetic diversity among Salmonella Enteritidis isolated from humans and animals in Malaysia
    Ngoi ST, Thong KL
    Diagn Microbiol Infect Dis, 2013 Dec;77(4):304-11.
    PMID: 24139970 DOI: 10.1016/j.diagmicrobio.2013.09.004
    Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common causative agent of non-typhoidal salmonellosis in Malaysia. We aimed to characterize S. Enteritidis isolated from humans and animals by analyzing their antimicrobial resistance profiles and genotypes. A total of 111 strains were characterized using multiple-locus variable-number tandem repeat analysis, pulsed-field gel electrophoresis, and antimicrobial susceptibility testing. Both typing methods revealed that genetically similar S. Enteritidis strains had persisted among human and animal populations within the period of study (2003-2008). Only 39% of the strains were multi-drug resistant (i.e., resistant to 3 or more classes of antimicrobial agents), with a majority (73%) of these in low-risk phase (multiple antibiotic resistant index <0.20). Limited genetic diversity among clinical and zoonotic S. Enteritidis suggested that animals are possible sources of human salmonellosis. The degree of multi-drug resistance among the strains was generally low during the study period.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  16. 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: Drug Resistance, Bacterial/genetics
  17. Fulltext Stenotrophomonas maltophilia in Malaysia: molecular epidemiology and trimethoprim-sulfamethoxazole resistance
    Neela V, Rankouhi SZ, van Belkum A, Goering RV, Awang R
    Int J Infect Dis, 2012 Aug;16(8):e603-7.
    PMID: 22698885 DOI: 10.1016/j.ijid.2012.04.004
    Stenotrophomonas maltophilia is a recently identified nosocomial pathogen in Malaysia. Despite limited pathogenicity, its rate of isolation has increased in recent years. The aim of this study was to investigate the antibiotic susceptibility patterns, antibiotic resistance determinants, and the epidemiology of S. maltophilia at the largest tertiary care hospital in Malaysia.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  18. Fulltext Molecular characterization of extended-spectrum β-lactamase-producing Klebsiella pneumoniae from a Malaysian hospital
    Mobasseri G, Thong KL, Rajasekaram G, Teh CSJ
    Braz J Microbiol, 2020 Mar;51(1):189-195.
    PMID: 31838661 DOI: 10.1007/s42770-019-00208-w
    Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae associated with nosocomial infections have caused serious problems in antibiotic management with limited therapeutic choices. This study aimed to determine the genotypic and phenotypic characteristics of K. pneumoniae strains isolated from a tertiary hospital in Malaysia. Ninety-seven clinical K. pneumoniae strains were analyzed for antimicrobial susceptibility, all of which were sensitive to amikacin and colistin (except one strain), while 31.9 % and 27.8 % were MDR and ESBL producers, respectively. PCR and DNA sequencing of the amplicons indicated that the majority of MDR strains (26/27) were positive for blaTEM, followed by blaSHV (24/27), blaCTX-M-1 group (23/27), blaCTX-M-9 group (2/27), and mcr-1 (1/27). Thirty-seven strains were hypervirulent and PCR detection of virulence genes showed 38.1 %, 22.7 %, and 16.5 % of the strains were positive for K1, wabG, and uge genes, respectively. Genotyping by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) showed that these strains were genetically diverse and heterogeneous. Sequence types, ST23, ST22, and ST412 were the predominant genotypes. This is the first report of colistin-resistant K. pneumoniae among clinical strains associated with mcr-1 plasmid in Malaysia. The findings in this study have contributed to the effort in combating the increase in antimicrobial resistance by providing better understanding of genotypic characteristics and resistance mechanisms of the organisms.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  19. Anthropogenic impacts on sulfonamide residues and sulfonamide resistant bacteria and genes in Larut and Sangga Besar River, Perak
    Lye YL, Bong CW, Lee CW, Zhang RJ, Zhang G, Suzuki S, et al.
    Sci Total Environ, 2019 Oct 20;688:1335-1347.
    PMID: 31726563 DOI: 10.1016/j.scitotenv.2019.06.304
    The environmental reservoirs of sulfonamide (SA) resistome are still poorly understood. We investigated the potential sources and reservoir of SA resistance (SR) in Larut River and Sangga Besar River by measuring the SA residues, sulfamethoxazole resistant (SMXr) in bacteria and their resistance genes (SRGs). The SA residues measured ranged from lower than quantification limits (LOQ) to 33.13 ng L-1 with sulfadiazine (SDZ), sulfadimethoxine (SDM) and SMX as most detected. Hospital wastewater effluent was detected with the highest SA residues concentration followed by the slaughterhouse and zoo wastewater effluents. The wastewater effluents also harbored the highest abundance of SMXr-bacteria (107 CFU mL-1) and SRGs (10-1/16S copies mL-1). Pearson correlation showed only positive correlation between the PO4 and SMXr-bacteria. In conclusion, wastewater effluents from the zoo, hospital and slaughterhouse could serve as important sources of SA residues that could lead to the consequent emergence of SMXr-bacteria and SRGs in the river.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  20. Fulltext Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations
    Low YM, Chong CW, Yap IKS, Chai LC, Clarke SC, Ponnampalavanar S, et al.
    Pathog Glob Health, 2018 10;112(7):378-386.
    PMID: 30380366 DOI: 10.1080/20477724.2018.1538281
    The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
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