Displaying publications 1 - 20 of 219 in total

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  1. Fulltext Draft Genome Sequence of Klebsiella pneumoniae Isolate PR04
    Zulkifli MH, Teh LK, Lee LS, Zakaria ZA, Salleh MZ
    Genome Announc, 2013;1(4).
    PMID: 23950113 DOI: 10.1128/genomeA.00418-13
    Klebsiella pneumoniae PR04 was isolated from a patient hospitalized in Malaysia. The draft genome sequence of K. pneumoniae PR04 shows differences compared to the reference sequences of K. pneumoniae strains MGH 78578 and NTUH-K2044 in terms of their genomic structures.
    Matched MeSH terms: Klebsiella Infections; Klebsiella pneumoniae
  2. Fulltext Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae
    Zowawi HM, Forde BM, Alfaresi M, Alzarouni A, Farahat Y, Chong TM, et al.
    Sci Rep, 2015;5:15082.
    PMID: 26478520 DOI: 10.1038/srep15082
    Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-bla(OXA-181) mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics.
    Matched MeSH terms: Klebsiella pneumoniae
  3. Fulltext Diagnostic use of PCR in Carbapenamase-producing Enterobacteriaceae (CPE): An mproved method to overcome the presence of inhibitors for DNA extraction from blood cultures
    Zeti Norfidiyati Salmuna, Murnihayati Hassan, Habsah Hasan, Zakuan Zainy Deris
    Malaysian Journal of Medicine and Health Sciences, 2019;15(1):1-4.
    MyJurnal
    Carpanenamase-producing Enterobacteriaceae (CPE) has emerged as a threat to hospitalized patients. Phenotypic test such as Modified hodge test was less sensitive and specific especially to detect blaNDM-1 which is the most predominant genotype in this region. Nucleic acid amplification technology offers improved specificity and sensitivity. Failed amplification due to the presence of inhibitors is a limitation. In this study, we tried to use previous method described by Villumseen et al with some modification using another DNA extraction kit. Methods: Ten mls of sterile whole blood taken from nearly expired blood bag from blood bank was spiked with 200 μl of 0.5mcFarland bacterial suspension from thirty-six confirmed isolates of blaNDM-1 carbapenamase-producing Klebsiella pneumoniae in an aerobic Bactec Plus and incubated until the growth was detected. The blood specimen was subjected to DNA extraction method using Macherey-Nachel, Nucleospin® Blood QuickPure followed with multiplex PCR. Results: Out of the 36 isolates, 12 isolates revealed blaNDM-1 , 9 isolates revealed blaNDM-1 and blaOXA-48, 7 isolates revealed blaNDM-1, blaVIM and blaKPC genotypes that were amplified at cycle threshold of less than 30. Another 8 isolates could not pick up any genotypes possibly due to pipetting error as all the internal control were amplified. Eight true negative gram negative isolates underwent same procedure and none amplified at a cycle threshold less than 30. Conclusion: This modified method was proved to give a high yield of CPE genotypes with the cycle threshold was set at less than or equal to 30 and able to overcome the presence of PCR inhibitors.
    Matched MeSH terms: Klebsiella pneumoniae
  4. Fulltext Metagenomic data on Anadara granosa associated bacterial communities using culture dependent approaches and 16S rRNA sequencing
    Zarkasi KZ, Halim MA, Nazari TF, Daud F
    Data Brief, 2018 Aug;19:514-519.
    PMID: 29900350 DOI: 10.1016/j.dib.2018.05.052
    This article contains data on the bacterial communities and its diversity associated with Anadara granosa. The A. granosa samples were obtained from two major estuaries in Penang, Malaysia using a culture dependent and 16S rRNA Illumina sequencing approaches. A. granosa, a commercial blood cockles and popular seafoods, is fragile to the surrounding environments. Thus, our research focused to better understand the bacterial communities and it diversity in the A. granosa, as well as on the generation of a metagenomic library from A. granosa to further understanding on it diversity. The bacteria Vibrionaceae (34.1%) was predominant in the A. granosa from both environments followed by Enterobacteriaceae (33.3%) and Bacillaceae (16.75%). Vibrio sp., Klebsiella sp., and Bacillus subtilis were the most abundant species present. The data generated in this research is the first metagenomic examination of A. granosa and will provide as a baseline to understand the bacterial communities associated with A. granosa and its surrounding natural environments.
    Matched MeSH terms: Klebsiella
  5. Case report post-splenectomy sepsis in thalassemic patients
    Zarina AL, Hamidah A, Zulkifli SZ, Jamal R
    Southeast Asian J. Trop. Med. Public Health, 2005 Mar;36(2):471-3.
    PMID: 15916058
    Thalassemia is the commonest hemoglobinopathy in Malaysia. Patients with thalassemia major are transfusion dependent, and a large proportion of them will require splenectomy. As this particular group of patients is immunocompromized, overwhelming sepsis is a recognized complication. We report a series of three patients who all developed intra-abdominal abscesses following splenectomy.
    Matched MeSH terms: Klebsiella pneumoniae/isolation & purification
  6. Rational use of intravenous polymyxin B and colistin: A review
    Zakuan ZD, Suresh K
    Med J Malaysia, 2018 10;73(5):351-359.
    PMID: 30350826 MyJurnal
    Polymyxin B and colistin (polymyxin E) were introduced in clinical practice to treat Gram-negative infections in 1950s but their parenteral use waned in 1970s due to toxicity concerns. Resurgence of polymyxins use in Malaysia began approximately in 2009 due to a lack of treatment options for MDR Gram negative superbugs such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. However, limited experience and a lack of widespread availability of up-to-date dosing guidelines could potentially result in incorrect use of these last resort antibiotics by managing doctors. The recent report of polymyxin resistant strains is also a cause of concern. Herein, we discuss the importance of preserving the efficacy of polymyxins in hospitals, the similarities and differences between polymyxin B and colistin, issues pertaining to current use of polymxyins and strategies to improve polymyxins' prescription. Polymyxins should only be used to treat significant infections, in optimum doses and if possible, in combination with other antibiotics.
    Matched MeSH terms: Klebsiella pneumoniae
  7. Fulltext Screening for bacteriuria in Malaysian school children
    Zainal D, Baba A
    Singapore Med J, 1994 Aug;35(4):374-5.
    PMID: 7899895
    Urinary tract infection is the most common of bacterial infections. Screening children for asymptomatic bacteriuria to prevent pyelonephritis and renal scarring is widely recommended. In Malaysia no such attempt has been made to establish the prevalence of asymptomatic bacteriuria. Bacteriuria was screened among 44,816 healthy school children from three different districts in Kelantan. There were 23,132 boys and 21,684 girls. The prevalence of bacteriuria was 0.12% after second screening. Higher prevalence was seen in other reports.
    Matched MeSH terms: Klebsiella/isolation & purification
  8. High burden of Carbapenem-resistant Enterobacteriaceae (CRE) fecal carriage at a teaching hospital: cost-effectiveness of screening in low-resource setting
    Zaidah AR, Mohammad NI, Suraiya S, Harun A
    Antimicrob Resist Infect Control, 2017;6:42.
    PMID: 28473912 DOI: 10.1186/s13756-017-0200-5
    BACKGROUND: Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia.

    METHODS: A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR) assay was performed to determine the genotype.

    RESULTS: Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74%) were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%)], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%). CRE were mainly isolated from rectal swab (screening), 235/477 (49.3%); urine, 76/477 (15.9%); blood, 46/477 (9.6%) and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4%) showed positive detection of New Delhi metallo-β-lactamase 1 (NDM-1) gene (blaNDM1).

    CONCLUSION: The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.

    Matched MeSH terms: Klebsiella; Klebsiella pneumoniae
  9. Identification of Nasal Irrigation Bottle Contamination in Post Sinonasal Surgery
    Zahedi FD, Asmi NH, Husain S, Gendeh BS
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1837-1842.
    PMID: 31763256 DOI: 10.1007/s12070-017-1219-x
    Nasal irrigation is an effective and cheap method in managing post sinonasal surgery patients. It works by improving ciliary clearance and performing mechanical debridement of the thick crust, decreasing mucosal edema and reducing the inflammatory mediators. Presence of nasal irrigation bottle contamination and its effect on patients have been studied. The aim of this study is to prospectively identify the risk of contamination in the nasal irrigation bottle, fluid from the bottle and to correlate with endoscopic findings from the patients who had underwent sinonasal surgery. Swabs will be taken from the nasal irrigation bottle and patient's middle meatus before the surgery and at each post surgery visits (2 and 4 weeks). Patients will be advised to irrigate their nose three times per day post sinonasal surgery. During endoscopic examination of the patient's nasal cavity at 2 and 4 weeks, any evidence of infection will be noted and documented. Additionally, a swab of fluid irrigated from the nasal cavity collected during the clinic follow-ups will also be taken. The specimens will be sent to the Microbiology laboratory for standard culture and sensitivity test. A total of 27 patients completed the study and were divided into case (n = 15) and control (n = 12) groups. The CFU (colony-forming unit) value of the bacteria cultured from the nasal cavity and the nasal irrigation bottle was statistically significantly (P = 0.00) increased from the baseline to the second week follow-up in both groups but not from the second week to the fourth week follow-up. The majority of the swabs from the nasal cavity of the patients and the nasal irrigation bottles were positively cultured for Pseudomonas sp. group. Other groups of bacteria that were cultured were Enterobacter sp., Coagulase Negative Staphylococcus (CONS) and Klebsiella sp. Endoscopically, there was no clinical evidence of infection found in the nasal cavity of the patients. The nasal irrigation bottle that was used in the post sinonasal surgery treatment and for alleviation of symptoms of sinonasal diseases was found to have bacterial contamination from the swabs taken from the bottle. However, despite this finding there was not clinical evidence of infection noted from the nasal endoscopic examination. A simple and effective method of cleaning the bottle would be helpful to reduce the bacterial contamination for this useful treatment method.
    Matched MeSH terms: Klebsiella
  10. Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery
    Yuan X, Amarnath Praphakar R, Munusamy MA, Alarfaj AA, Suresh Kumar S, Rajan M
    Carbohydr Polym, 2019 Feb 15;206:1-10.
    PMID: 30553301 DOI: 10.1016/j.carbpol.2018.10.098
    Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.
    Matched MeSH terms: Klebsiella pneumoniae/drug effects
  11. Differential abundance and core members of the bacterial community associated with wild male Zeugodacus cucurbitae fruit flies (Insecta: Tephritidae) from three geographical regions of Southeast Asia
    Yong HS, Song SL, Eamsobhana P, Pasartvit A, Lim PE
    Mol Biol Rep, 2019 Aug;46(4):3765-3776.
    PMID: 31012029 DOI: 10.1007/s11033-019-04818-3
    Zeugodacus cucurbitae (Coquillet) is one of the most significant and widespread tephritid pest species of agricultural crops. This study reports the bacterial communities associated with Z. cucurbitae from three geographical regions in Southeast Asia (Thailand, Peninsular Malaysia, and Sarawak). The bacterial microbiota were investigated by targeted 16S rRNA gene (V3-V4 region) sequencing using the Illumina Mi-Seq platform. At 97% similarity and filtering at 0.001%, there were seven bacterial phyla and unassigned bacteria, comprising 11 classes, 23 orders, 39 families and 67 genera. The bacterial diversity and richness varied within and among the samples from the three geographical regions. Five phyla were detected for the Sarawak sample, and six each for the Thailand and Peninsular Malaysia samples. Four phyla-Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria-were represented in all the fruit fly specimens, forming the core members of the bacterial community. Proteobacteria was the predominant phylum, followed by Bacteroidetes, Firmicutes, and Actinobacteria. Fifty-three genera were represented in the Thailand sample, 56 in the Peninsular Malaysia sample, and 55 in the Sarawak sample. Forty-two genera were present in all the three geographical regions. The predominant core members were order Enterobacteriales (Proeteobacteria), and family Enterobacteriaceae (Enterobacteriales). Klebsiella (Enterobacteriaceae) was the predominant genus and K. oxytoca the predominant species with all specimens having > 10% relative abundance. The results indicate the presence of a great diversity as well as core members of the bacterial community associated with different populations of Z. cucurbitae.
    Matched MeSH terms: Klebsiella/genetics
  12. Fulltext Bacteriology of diabetic foot lesions
    Yoga R, Khairul A, Sunita K, Suresh C
    Med J Malaysia, 2006 Feb;61 Suppl A:14-6.
    PMID: 17042222
    Infection plays a pivotal role in enhancing a diabetic foot at risk toward amputation. Effective antibiotic therapy against the offending pathogens is an important component of treatment of diabetic foot infections. Recognition of the pathogen is always difficult as the representative deep tissue sample for culture is surrounded by ulcer surface harbouring colonies of organisms frequently labelled as skin commensals. The emergent of resistant strains represents a compounding problem standing against efforts to prevent amputation. This study was undertaken to identify the pathogens associated with diabetic foot infection in terms of their frequency and sensitivity against certain commonly used antibiotics. Forty-four consecutive patients with open diabetic foot infections had wound swab taken for culture and sensitivity testing. Cultures positive were observed in 89% of the cases with Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeroginosa encountered in 20%, 14% and 14% of cases respectively. Mixed growths were isolated in 6% of cultures. All Staphylcoccus aureus isolates were resistant to Penicillin but 80% were sensitive to Erythromycin and Co-trimoxazole. Klebsiella pneumoniae isolates were sensitive to Methicillin and Gentamycin in 80% and 60% of cases respectively, and resistant to Ampicillin and Ceftazidime in 83% and 50% respectively. All Pseudomonas aeroginosa isolates were sensitive to Amikacin and Ciprofloxacin but 50% were resistant to Gentamycin. There was no single antibiotic possessing good coverage for all common organisms isolated from diabetic foot lesions. Staphylococcus aureus remains the predominant cause of diabetic foot infections followed by Klebsiela pneumonia and Pseudomonas aeroginosa. Most infections are monomicrobial. The emergence of multiresistant organisms is a worrying feature in diabetic foot infections.
    Matched MeSH terms: Klebsiella pneumoniae/isolation & purification*
  13. Fulltext N-acyl homoserine lactone production by Klebsiella pneumoniae isolated from human tongue surface
    Yin WF, Purmal K, Chin S, Chan XY, Koh CL, Sam CK, et al.
    Sensors (Basel), 2012;12(3):3472-83.
    PMID: 22737019 DOI: 10.3390/s120303472
    Bacteria communicate by producing quorum sensing molecules called autoinducers, which include autoinducer-1, an N-hexanoyl homoserine lactone (AHL), and autoinducer-2. Bacteria present in the human oral cavity have been shown to produce autoinducer-2, but not AHL. Here, we report the isolation of two AHL-producing Klebsiella pneumoniae strains from the posterior dorsal surface of the tongue of a healthy individual. Spent culture supernatant extracts from K. pneumoniae activated the biosensors Agrobacterium tumefaciens NTL4(pZLR4) and Escherichia coli [pSB401], suggesting the presence of both long and short chain AHLs. High resolution mass spectrometry analyses of these extracts confirmed that both K. pneumoniae isolates produced N-octanoylhomoserine lactone and N-3-dodecanoyl-L-homoserine lactone. To the best of our knowledge, this is the first report of the isolation of K. pneumoniae from the posterior dorsal surface of the human tongue and the production of these AHLs by this bacterium.
    Matched MeSH terms: Klebsiella pneumoniae/classification; Klebsiella pneumoniae/isolation & purification*; Klebsiella pneumoniae/metabolism
  14. GNAT toxins of bacterial toxin-antitoxin systems: acetylation of charged tRNAs to inhibit translation
    Yeo CC
    Mol Microbiol, 2018 05;108(4):331-335.
    PMID: 29624768 DOI: 10.1111/mmi.13958
    GCN5-related N-acetyltransferase (GNAT) is a huge superfamily of proteins spanning the prokaryotic and eukaryotic domains of life. GNAT proteins usually transfer an acetyl group from acetyl-CoA to a wide variety of substrates ranging from aminoglycoside antibiotics to large macromolecules. Type II toxin-antitoxin (TA) modules are typically bicistronic and widespread in bacterial and archael genomes with diverse cellular functions. Recently, a novel family of type II TA toxins was described, which presents a GNAT-fold and functions by acetylating charged tRNA thereby precluding translation. These GNAT toxins are usually associated with a corresponding ribbon-helix-helix-fold (RHH) antitoxin. In this issue, Qian et al. describes a unique GNAT-RHH TA system, designated KacAT, from a multidrug resistant strain of the pathogen, Klebsiella pneumoniae. As most type II TA loci, kacAT is transcriptionally autoregulated with the KacAT complex binding to the operator site via the N-terminus region of KacA to repress kacAT transcription. The crystal structure of the KacT toxin is also presented giving a structural basis for KacT toxicity. These findings expand our knowledge on this newly discovered family of TA toxins and the potential role that they may play in antibiotic tolerance and persistence of bacterial pathogens.
    Matched MeSH terms: Klebsiella pneumoniae*
  15. Genomic Insights into Two Colistin-Resistant Klebsiella pneumoniae Strains Isolated from the Stool of Preterm Neonate During the First Week of Life
    Yap PSX, Ahmad Kamar A, Chong CW, Ngoi ST, Teh CSJ
    Microb Drug Resist, 2020 Mar;26(3):190-203.
    PMID: 31545116 DOI: 10.1089/mdr.2019.0199
    Background:
    Klebsiella pneumoniae is a major opportunistic pathogen frequently associated with nosocomial infections, and often poses a major threat to immunocompromised patients. In our previous study, two K. pneumoniae (K36 and B13), which displayed resistance to almost all major antibiotics, including colistin, were isolated. Both isolates were not associated with infection and isolated from the stools of two preterm neonates admitted to the neonatal intensive care unit (NICU) during their first week of life.
    Materials and Methods:
    In this study, whole genome sequencing was performed on these two clinical multidrug resistant K. pneumoniae. We aimed to determine the genetic factors that underline the antibiotic-resistance phenotypes of these isolates.
    Results:
    The strains harbored blaSHV-27, blaSHV-71, and oqxAB genes conferring resistance to cephalosporins, carbapenems, and fluoroquinolones, respectively, but not harboring any known plasmid-borne colistin resistance determinants such as mcr-1. However, genome analysis discovered interruption of mgrB gene by insertion sequences gaining insight into the development of colistin resistance.
    Conclusion:
    The observed finding that points to a scenario of potential gut-associated resistance genes to Gram negative (K. pneumoniae) host in the NICU environment warrants attention and further investigation.
    Matched MeSH terms: Klebsiella Infections/microbiology; Klebsiella Infections/pathology; Klebsiella pneumoniae/drug effects; Klebsiella pneumoniae/genetics*; Klebsiella pneumoniae/isolation & purification; Klebsiella pneumoniae/pathogenicity*
  16. Intestinal carriage of multidrug-resistant gram-negative bacteria in preterm-infants during hospitalization in neonatal intensive care unit (NICU)
    Yap PS, Ahmad Kamar A, Chong CW, Yap IK, Thong KL, Choo YM, et al.
    Pathog Glob Health, 2016 Sep;110(6):238-246.
    PMID: 27650884
    The prevalence and antibiotic susceptibility of intestinal carriage of Gram-negative bacteria among preterm infants admitted to the neonatal intensive care unit (NICU) in a tertiary teaching hospital in Malaysia were determined. A total of 34 stool specimens were obtained from preterm infants upon admission and once weekly up to two weeks during hospitalization. The presumptive colonies of Escherichia coli and Klebsiella pneumoniae were selected for identification, antibiotic susceptibility testing, and subtyping by using pulsed-field gel electrophoresis (PFGE). Out of 76 Gram-negative isolates, highest resistance was detected for amoxicillin/clavulanate (30.8%, n = 16), ceftriaxone (42.3%, n = 22), ceftazidime (28.8%, n = 15), cefoxitin (28.8%, n = 15), aztreonam (36.5%, n = 19), and polymyxin B (23.1%, n = 12). Three colistin resistant K. pneumoniae have also been detected based on E-test analysis. Thirty-nine isolates of K. pneumoniae and 20 isolates of E. coli were resistant to more than three antimicrobial classes and were categorized as multidrug resistant (MDR). PFGE analysis revealed a higher diversity in pulsotypes for K. pneumoniae (18 pulsotypes) in comparison to E. coli (four pulsotypes). In addition, a total of fifteen pulsotypes was observed from 39 MDR K. pneumoniae. The risk factors for antibiotic resistance were assessed using random forest analysis. Gender was found to be the most important predictor for colistin resistant while length, OFC, and delivery mode were showing greater predictive power in the polymyxin B resistance. This study revealed worrying prevalence rates of intestinal carriage of multidrug-resistant K. pneumoniae and E. coli of hospitalized preterm infants in Malaysia, particularly high resistance to polymyxins.
    Matched MeSH terms: Klebsiella pneumoniae/drug effects; Klebsiella pneumoniae/isolation & purification
  17. 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: Klebsiella pneumoniae/genetics; Klebsiella pneumoniae/metabolism
  18. Fulltext Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
    Yang SK, Yusoff K, Ajat M, Wee CY, Yap PS, Lim SH, et al.
    Front Microbiol, 2021;12:635016.
    PMID: 33815320 DOI: 10.3389/fmicb.2021.635016
    Antibiotic-adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Linalool exhibited bactericidal activity alone (11,250 μg/ml) and in combination with meropenem (5,625 μg/ml). Comparative proteomic analysis showed significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in linalool-treated KPC-KP cells. Upregulation of oxidative stress regulator proteins and downregulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that linalool increases the bacterial surface charge as well as the membrane permeability. Intracellular leakage of nucleic acid and proteins was detected upon linalool treatment. Scanning and transmission electron microscopies further revealed the breakage of bacterial membrane and loss of intracellular materials. Linalool induced oxidative stress by generating reactive oxygen species (ROS) which initiates lipid peroxidation, leading to damage of the bacterial membrane. This leads to intracellular leakage, eventually killing the KPC-KP cells. Our study demonstrated that linalool possesses great potential in future clinical applications as an adjuvant along with existing antibiotics attributed to their ability in disrupting the bacterial membrane by inducing oxidative stress. This facilitates the uptake of antibiotics into the bacterial cells, enhancing bacterial killing.
    Matched MeSH terms: Klebsiella pneumoniae
  19. Fulltext Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae
    Yang SK, Yusoff K, Thomas W, Akseer R, Alhosani MS, Abushelaibi A, et al.
    Sci Rep, 2020 01 21;10(1):819.
    PMID: 31964900 DOI: 10.1038/s41598-019-55601-0
    Misuse of antibiotics in the clinical and agricultural sectors has caused the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae which contributes a threat to human health. In this study, we assessed the feasibility of lavender essential oil (LVO) as an antimicrobial agent in combinatory therapy with meropenem in suppressing the growth of carbapenemase-producing K. pneumoniae (KPC-KP). Synergistic interactions between LVO and meropenem were detected, which significantly reduce the inhibitory concentration of both LVO and meropenem by 15 and 4-fold respectively. Comparative proteomic profiling identified a disruption in the bacterial membrane via oxidative stress that was indicated by loss of membrane and cytoplasmic proteins and the upregulation of oxidative regulators. As a proof of concept, zeta potential measurements showed a change in cell surface charge while outer membrane permeability measurement indicated an increase in membrane permeability following exposure to LVO. This was indicative of a disrupted outer membrane. Ethidium bromide influx/efflux assays demonstrated no significant efflux pump inhibition by LVO, and scanning electron microscopy revealed irregularities on the cell surface after exposure to LVO. Oxidative stress was also detected with increased level of ROS and lipid peroxidation in LVO-treated cells. In conclusion, our data suggest that LVO induced oxidative stress in K. pneumoniae which oxidizes the outer membrane, enabling the influx of generated ROS, LVO and meropenem into the bacterial cells, causing damage to the cells and eventually death.
    Matched MeSH terms: Klebsiella pneumoniae/cytology; Klebsiella pneumoniae/drug effects*; Klebsiella pneumoniae/growth & development; Klebsiella pneumoniae/metabolism
  20. Fulltext Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae
    Yang SK, Yusoff K, Ajat M, Yap WS, Lim SE, Lai KS
    J Pharm Anal, 2021 Apr;11(2):210-219.
    PMID: 34012697 DOI: 10.1016/j.jpha.2020.05.014
    Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.
    Matched MeSH terms: Klebsiella pneumoniae
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