scholarly journals Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan

2015 ◽  
Vol 59 (5) ◽  
pp. 2909-2913 ◽  
Author(s):  
Yi-Hsiang Cheng ◽  
Tzu-Lung Lin ◽  
Yi-Jiun Pan ◽  
Yu-Ping Wang ◽  
Yi-Tsung Lin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Resistance Mechanisms ◽  
Single Amino Acid ◽  
Colistin Resistance ◽  
Amino Acid Mutation ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Sequence Types

ABSTRACTColistin is one of the antibiotics of last resort for the treatment of carbapenem-resistantKlebsiella pneumoniaeinfection. This study showed that capsular type K64 (50%) and ST11 (53.9%) are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan. The interruption of transcripts (38.5%) and amino acid mutation (15.4%) inmgrBare the major mechanisms contributing to colistin resistance. In addition, novel single amino acid changes in MgrB (Stop48Tyr) and PhoQ (Leu26Pro) were observed to contribute to colistin resistance.

scholarly journals Amino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae

2016 ◽  
Vol 60 (6) ◽  
pp. 3709-3716 ◽  
Author(s):  
Yi-Hsiang Cheng ◽  
Tzu-Lung Lin ◽  
Yi-Tsung Lin ◽  
Jin-Town Wang
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Site Directed Mutagenesis ◽  
Amino Acid Substitutions ◽  
Missense Mutations ◽  
Colistin Resistance ◽  
Two Component System ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Elevated Expression

Colistin is a last-resort antibiotic for treatment of carbapenem-resistantKlebsiella pneumoniae. A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistantK. pneumoniaeclinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study,crrABsequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generatecrrBloci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. ThesecrrBmutants showed increased accumulation ofH239_3062,H239_3059,pmrA,pmrC, andpmrHtranscripts by quantitative reverse transcription (qRT)-PCR. Deletion ofH239_3062(but not that ofH239_3059) in the A4528crrB(N141I) strain attenuated resistance to colistin, andH239_3062was accordingly namedcrrC. Similarly, accumulation ofpmrA,pmrC, andpmrHtranscripts induced bycrrB(N141I) was significantly attenuated upon deletion ofcrrC. Complementation ofcrrCrestored resistance to colistin and accumulation ofpmrA,pmrC, andpmrHtranscripts in acrrB(N141I) ΔcrrCstrain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of thepmrHFIJKLMoperon andpmrC(an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance.

scholarly journals Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Astrid V. Cienfuegos-Gallet ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
J. Natalia Jiménez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Plasmid Dna ◽  
Clonal Expansion ◽  
Genetic Alterations ◽  
Sequence Type ◽  
Chromosomal Integration ◽  
Colistin Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Single Locus Variant

ABSTRACT Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

scholarly journals Draft Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae XPY20 Collected from a Bloodstream Infection Patient

2018 ◽  
Vol 6 (21) ◽  
Author(s):  
Qiong Chen ◽  
Jia-wei Zhou ◽  
Sheng-hai Wu ◽  
Xiao-hua Meng ◽  
Dao-jun Yu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Draft Genome ◽  
Bloodstream Infections ◽  
Mortality Rates ◽  
Resistance Mechanisms ◽  
Severe Problem ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Infection Patient ◽  
Generation Sequencing

ABSTRACT Bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have been a severe problem with high clinical costs and high mortality rates. The bla KPC-2-producing CRKP strain XPY20 was collected from the blood of a patient. The genome characteristics and antimicrobial resistance mechanisms were determined using next-generation sequencing.

scholarly journals Fighting Antibiotic-Resistant Klebsiella pneumoniae with “Sweet” Immune Targets

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Therapeutic Approaches ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Surface Polysaccharides ◽  
Resistant Strains ◽  
Murine Monoclonal Antibodies

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.

scholarly journals In Vivo Efficacy of Novel Monobactam LYS228 in Murine Models of Carbapenemase-Producing Klebsiella pneumoniae Infection

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
W. J. Weiss ◽  
M. E. Pulse ◽  
P. Nguyen ◽  
E. J. Growcott
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Development ◽  
Murine Models ◽  
Bacterial Burden ◽  
In Vivo Efficacy ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Infection Models ◽  
Resistant Strains

ABSTRACT LYS228 has potent antibacterial activity against carbapenem-resistant strains of Enterobacteriaceae. LYS228 was efficacious in neutropenic thigh models established with Klebsiella pneumoniae producing KPC-2 or NDM-1; pretreatment with uranyl nitrate considerably shifted calculated static doses of LYS228. In murine ascending pyelonephritis, LYS228 reduced bacterial burden in kidney, urine, and bladder. The successful treatment of murine infection models established with carbapenem-resistant K. pneumoniae further supports the clinical development of LYS228.

scholarly journals Molecular Epidemiology of Staphylococcus epidermidis Clinical Isolates from U.S. Hospitals

2012 ◽  
Vol 56 (9) ◽  
pp. 4656-4661 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Lalitagauri M. Deshpande ◽  
Andrew J. Costello ◽  
David J. Farrell
Keyword(s):  
Staphylococcus Epidermidis ◽  
Resistance Mechanisms ◽  
23S Rrna ◽  
Content Type ◽  
Linezolid Resistance ◽  
Clonal Distribution ◽  
Resistant Strains ◽  
Resistance Rates ◽  
Susceptibility Profiles ◽  
Sequence Types

ABSTRACTThe epidemiology ofStaphylococcus epidermidisin U.S. hospitals remains limited. This study aimed to address the genetic backgrounds of linezolid-susceptible and -resistantS. epidermidisstrains (isolated in 2010), includingcfr-carrying strains. In addition, the antimicrobial susceptibility profiles and linezolid resistance mechanisms among clonal lineages were assessed. A total of 71S. epidermidisisolates were selected, and linezolid-resistant strains were screened forcfrand mutations in 23S rRNA, L3, and L4. All isolates were subjected to multilocus sequence typing (MLST), and the results were analyzed by eBURST. Overall, 27 sequence types (STs) were detected, and ST5 (21.1%) and ST2 (16.9%) predominated. The majority (62/71; 87.3%) of STs belonged to clonal complex 2 (CC2), which was mostly comprised of subclusters CC2-II (41/62; 66.1%) and CC2-I (21/62; 33.9%). Other STs were grouped within CC23 or CC32 or were singletons. CC2-I strains were more likely to display a methicillin (95.2% versus 33.3 to 70.7%), a linezolid (47.6% versus 0.0 to 7.3%), or a multidrug (81.0% versus 33.3 to 36.6%) resistance phenotype. Among linezolid-resistant isolates,cfrwas noted only within CC2 strains, and it was detected equally in the CC2-I (3/10; 30.0%) and CC2-II (1/3; 33.3%) subclusters. 23S rRNA mutations (G2576 [seven strains] and C2534 [one strain]) were observed only among CC2-I (8/10; 80.0%) isolates. Strains showing a G2576 alteration also had M156 (7/7; 100.0%) and/or H146 (6/7; 85.7%) L3 modifications. This study provides an overview of theS. epidermidisclonal distribution and reports higher resistance rates among CC2-I strains. The results show thatcfrmay be acquired and expressed by both CC2 main subclusters, while 23S rRNA mutations appeared more often within CC2-I strains. Interestingly, these 23S rRNA mutants also had L3 alterations, which may act synergistically or in a compensatory manner to minimize the fitness cost while providing survival advantages under selective pressure.

scholarly journals The Acquisition of Colistin Resistance Is Associated to the Amplification of a Large Chromosomal Region in Klebsiella pneumoniae kp52145

2021 ◽  
Vol 22 (2) ◽  
pp. 649
Author(s):  
María Blanca Sánchez ◽  
Alicia Sánchez-Gorostiaga ◽  
Trinidad Cuesta ◽  
José Luis Martínez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Experimental Evolution ◽  
Chromosomal Region ◽  
Genetic Change ◽  
Cross Resistance ◽  
Common Mutation ◽  
Colistin Resistance ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Resistant Strains

The appearance of carbapenem-resistant Klebsiella pneumoniae has increased the use of colistin as a last-resort antibiotic for treating infections by this pathogen. A consequence of its use has been the spread of colistin-resistant strains, in several cases carrying colistin resistance genes. In addition, when susceptible strains are confronted with colistin during treatment, mutation is a major cause of the acquisition of resistance. To analyze the mechanisms of resistance that might be selected during colistin treatment, an experimental evolution assay for 30 days using as a model the clinical K. pneumoniae kp52145 isolate in the presence of increasing amounts of colistin was performed. All evolved populations presented a decreased susceptibility to colistin, without showing cross-resistance to antibiotics belonging to other structural families. We did not find any common mutation in the evolved mutants, neither in already known genes, previously known to be associated with the resistance phenotype, nor in new ones. The only common genetic change observed in the strains that evolved in the presence of colistin was the amplification of a 34 Kb sequence, homologous to a prophage (Enterobacteria phage Fels-2). Our data support that gene amplification can be a driving force in the acquisition of colistin resistance by K. pneumoniae.

scholarly journals Rapid Increase in Prevalence of Carbapenem-ResistantEnterobacteriaceae(CRE) and Emergence of Colistin Resistance Genemcr-1in CRE in a Hospital in Henan, China

2018 ◽  
Vol 56 (4) ◽  
Author(s):  
Yi Li ◽  
Qiao-ling Sun ◽  
Yingbo Shen ◽  
Yangjunna Zhang ◽  
Jun-wen Yang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Clinical Samples ◽  
New Delhi ◽  
Colistin Resistance ◽  
Large Hospital ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Recent Emergence ◽  
Almost All

ABSTRACTThe global spread of carbapenem-resistantEnterobacteriaceae(CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance genemcr-1among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249Enterobacteriaceaeisolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistantKlebsiella pneumoniaeand carbapenem-resistantEscherichia coliwere the two most common CRE species, withKlebsiella pneumoniaecarbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% (n= 589) of theK. pneumoniaeisolates from the intensive care unit were carbapenem resistant. Furthermore,blaNDM-5andmcr-1were found to coexist in oneE. coliisolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused byK. pneumoniaein the studied hospital.

scholarly journals Effect of Resistance Mechanisms on the Inoculum Effect of Carbapenem in Klebsiella pneumoniae Isolates with Borderline Carbapenem Resistance

2015 ◽  
Vol 59 (8) ◽  
pp. 5014-5017 ◽  
Author(s):  
Amos Adler ◽  
Ma'ayan Ben-Dalak ◽  
Ina Chmelnitsky ◽  
Yehuda Carmeli
Keyword(s):  
Klebsiella Pneumoniae ◽  
Therapeutic Efficacy ◽  
Carbapenem Resistance ◽  
Bactericidal Effect ◽  
Resistance Mechanisms ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Inoculum Effect

ABSTRACTWe aimed to examine the effects of resistance mechanisms on several resistance phenotypes among carbapenem-resistantKlebsiella pneumoniaeisolates with borderline carbapenem MICs. We compared carbapenemase-negativeK. pneumoniaewith carbapenemase-producingK. pneumoniae(CPKP) isolates with similar MICs. CPKP isolates exhibited a marked inoculum effect and were more resistant to the bactericidal effect of meropenem. This suggests that MIC measurements alone may not be sufficient in predicting the therapeutic efficacy of carbapenems against CPKP.

scholarly journals Identification of Capsular Types in Carbapenem-Resistant Klebsiella pneumoniae Strains bywzcSequencing and Implications for Capsule Depolymerase Treatment

2014 ◽  
Vol 59 (2) ◽  
pp. 1038-1047 ◽  
Author(s):  
Yi-Jiun Pan ◽  
Tzu-Lung Lin ◽  
Yi-Tsung Lin ◽  
Po-An Su ◽  
Chun-Tang Chen ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Vaccine Development ◽  
Survival Rates ◽  
Multidrug Resistant ◽  
Enzyme Treatment ◽  
Capsular Type ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Sequence Types

ABSTRACTKlebsiella pneumoniaeis an important human pathogen associated with a variety of diseases, and the prevalence of multidrug-resistantK. pneumoniae(MDRKP) is rapidly increasing. Here we determined the capsular types of 85 carbapenem-resistantK. pneumoniae(CRKP) strains bywzcsequencing and investigated the presence of carbapenemases and integrons among CRKP strains. Ten CRKP strains (12%) were positive for carbapenemase (imipenemase, 6/85 strains;K. pneumoniaecarbapenemase, 3/85 strains; Verona integron-encoded metallo-β-lactamase, 1/85 strains). Capsular type K64 accounted for 32 CRKP strains (38%), followed by K62 (13%), K24 (8%), KN2 (7%), and K28 (6%). Sequence types (STs) were determined by multilocus sequence typing (MLST), and the results indicated that ST11, which accounted for 47% of these CRKP strains (40/85 strains), was the major ST. We further isolated a K64-specific capsule depolymerase (K64dep), which could enhance serum and neutrophil killingin vitroand increase survival rates for K64K. pneumoniae-inoculated mice. The toxicity study demonstrated that mice treated with K64dep showed normal biochemical parameters and no significant histopathological changes of liver, kidney, and spleen, indicating that enzyme treatment did not cause toxicity in mice. Therefore, the findings of capsular type clustering among CRKP strains and effective treatment with capsule depolymerase for MDRKP infections are important for capsule-based vaccine development and therapy.

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