scholarly journals Analysis of the Oxidative Stress Regulon Identifies soxS as a Genetic Target for Resistance Reversal in Multidrug-Resistant Klebsiella pneumoniae

mBio ◽  
2021 ◽  
Author(s):  
João Anes ◽  
Katherine Dever ◽  
Athmanya Eshwar ◽  
Scott Nguyen ◽  
Yu Cao ◽  
...  
Keyword(s):  
Public Health ◽  
Oxidative Stress ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Global Health ◽  
Multidrug Resistant ◽  
Content Type ◽  
Resistance Reversal ◽  
New Antibiotics ◽  
Global Health Challenge

Antimicrobial resistance is a global health challenge. Few new antibiotics have been developed for use over the years, and preserving the efficacy of existing compounds is an important step to protect public health. This paper describes a study that examines the effects of exogenously induced oxidative stress on K. pneumoniae and uncovers a target that could be useful to harness as a strategy to mitigate resistance.

scholarly journals Lack of Antimicrobial Resistance in Yersinia pestis Isolates from 17 Countries in the Americas, Africa, and Asia

2011 ◽  
Vol 56 (1) ◽  
pp. 555-558 ◽  
Author(s):  
Sandra K. Urich ◽  
Linda Chalcraft ◽  
Martin E. Schriefer ◽  
Brook M. Yockey ◽  
Jeannine M. Petersen
Keyword(s):  
Public Health ◽  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Yersinia Pestis ◽  
Causative Agent ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Health Concern ◽  
Public Health Concern ◽  
Content Type

ABSTRACTYersinia pestisis the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance inY. pestiswas reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392Y. pestisisolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.

scholarly journals Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare blaCTX-M-24-Harboring Virulence Plasmid

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Dingxia Shen ◽  
Guannan Ma ◽  
Cuidan Li ◽  
Xinmiao Jia ◽  
Chuan Qin ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Genetic Basis ◽  
Virulence Genes ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Hybrid Plasmid ◽  
Virulence Plasmid ◽  
Drug Resistant ◽  
Content Type

ABSTRACT Here, we report a multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-HvKP) strain of sequence type 23 (ST23) with a rare hybrid plasmid harboring virulence genes and blaCTX-M-24, and we analyze the genetic basis for relationship between genotypes and MDR-hypervirulence phenotypes. Further analysis indicates that the hybrid plasmid is formed by IS903D-mediated intermolecular transposition of the blaCTX-M-24 gene into the virulence plasmid. The emergence of MDR-HvKP strains, especially those carrying drug-resistant virulent plasmids, poses unprecedented threats/challenges to public health. This is a dangerous trend and should be closely monitored.

scholarly journals Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Weihua Huang ◽  
Guiqing Wang ◽  
Robert Sebra ◽  
Jian Zhuge ◽  
Changhong Yin ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
De Novo ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Comparative Genomic ◽  
Type I ◽  
Content Type ◽  
Antimicrobial Resistance Genes

ABSTRACT The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both bla CTX-M and bla KPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, bla CTX-M and bla KPC were carried on two different plasmids. In contrast, CN1 had one copy of bla KPC-2 and three copies of bla CTX-M-15 integrated in the chromosome, for which the bla CTX-M-15 genes were linked to an insertion sequence, ISEcp1, whereas the bla KPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-bla KPC-2-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested that the evolving CRISPR-cas, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of bla CTX-M and bla KPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae. Additionally, the implications from this study also raise concerns for the application of a CRISPR-cas strategy against antimicrobial resistance.

scholarly journals Genomic Analysis of a Pan-Resistant Isolate ofKlebsiella pneumoniae, United States 2016

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Tom J. B. de Man ◽  
Joseph D. Lutgring ◽  
David R. Lonsway ◽  
Karen F. Anderson ◽  
Julia A. Kiehlbauch ◽  
...  
Keyword(s):  
Public Health ◽  
United States ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
The United States ◽  
Whole Genome ◽  
Beta Lactams ◽  
Content Type

ABSTRACTAntimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusualKlebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. patient. The isolate harbored four known beta-lactamase genes, including plasmid-mediatedblaNDM-1andblaCMY-6, as well as chromosomalblaCTX-M-15andblaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the firstK. pneumoniaeisolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCEAntimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. AKlebsiella pneumoniaestrain that was nonsusceptible to all tested antibiotics was isolated from a U.S. patient. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.

scholarly journals KlebSeq, a Diagnostic Tool for Surveillance, Detection, and Monitoring of Klebsiella pneumoniae

2016 ◽  
Vol 54 (10) ◽  
pp. 2582-2596 ◽  
Author(s):  
Jolene R. Bowers ◽  
Darrin Lemmer ◽  
Jason W. Sahl ◽  
Talima Pearson ◽  
Elizabeth M. Driebe ◽  
...  
Keyword(s):  
Public Health ◽  
Health Care ◽  
Klebsiella Pneumoniae ◽  
Group Identification ◽  
Amplicon Sequencing ◽  
Multidrug Resistant ◽  
Care Staff ◽  
Health Care Staff ◽  
Health Crisis ◽  
Content Type

Health care-acquired infections (HAIs) kill tens of thousands of people each year and add significantly to health care costs. Multidrug-resistant and epidemic strains are a large proportion of HAI agents, and multidrug-resistant strains ofKlebsiella pneumoniae, a leading HAI agent, have caused an urgent public health crisis. In the health care environment, patient colonization byK. pneumoniaeprecedes infection, and transmission via colonization leads to outbreaks. Periodic patient screening forK. pneumoniaecolonization has the potential to curb the number of HAIs. In this report, we describe the design and validation of KlebSeq, a highly informative screening tool that detectsKlebsiellaspecies and identifies clinically important strains and characteristics by using highly multiplexed amplicon sequencing without a live-culturing step. We demonstrate the utility of this tool on several complex specimen types, including urine, wound swabs and tissue, and several types of respiratory and fecal specimens, showingK. pneumoniaespecies and clonal group identification and antimicrobial resistance and virulence profiling, including capsule typing. Use of this amplicon sequencing tool to screen patients forKlebsiellacarriage could inform health care staff of the risk of infection and outbreak potential. KlebSeq also serves as a model for next-generation molecular tools for public health and health care, as expansion of this tool can be used for several other HAI agents or applications.

scholarly journals Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Yi-Tsung Lin ◽  
Yi-Hsiang Cheng ◽  
Chien Chuang ◽  
Sheng-Hua Chou ◽  
Wan-Hsin Liu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Virulence Plasmid ◽  
Content Type ◽  
Sequence Types

ABSTRACT Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

Multidrug-resistant Klebsiella pneumoniae: risks to food safety and public health

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Cornacchia ◽  
V Di Marzio ◽  
A Ciarrocchi ◽  
M A Saletti ◽  
C Marfoglia ◽  
...  
Keyword(s):  
Public Health ◽  
Food Safety ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Illumina Platform ◽  
Aminoglycoside Resistance ◽  
Consumer Safety

Abstract Background Klebsiella pneumoniae (Kp) is a Gram-negative hospital-acquired pathogen. Kp also poses a potential food safety hazard, since a significant increase of multidrug-resistant (MDR) Kp was observed in foods. The purpose of this study was to characterize MDR Kp strains in order to evaluate the presence of beta-lactams, quinolones and aminoglycosides resistance genes. Methods A total of 13 Kp strains, isolated from chicken (n.8), raw milk (n.2), waste water (n.2), human faeces (n.1), and identified as MDR by microdilution test, were selected to evaluate antimicrobial resistance profiles, focusing on beta-lactams, quinolones and aminoglycosides. Next Generation Sequencing (NGS), with NextSeq 500 Illumina platform, was performed to acquire genome sequences. The antimicrobial resistance profiles were obtained using ResFinder (https://cge.cbs.dtu.dk/services/ResFinder/). Results From the 13 Kp considered, 6 strains (46.2 %) showed the presence of several beta-lactam genes. The blaSHV gene was carried by 12 Kp (92.3%); of these strains, 5 also carried blaTEM (41.7%) and 3 also blaCTX-M (25.0%) genes. Only 1 Kp strain showed the presence of blaOKP-A gene. All the 13 Kp carried the oqxA and oqxB genes. Of these strains, 4 also highlighted the presence of qnrB or qnrS plasmid-mediated gene for quinolone resistance. Regarding aminoglycoside resistance, 6 Kp strains (46.2%) carried aph, aadA and aaC genes, linked to gentamicin and streptomycin resistance protein. Conclusions These preliminary results emphasize the need of further studies on more several samples, to better understand the antimicrobial resistance of Kp strains, the hypothetical transmission of MDR Kp from foods to consumers and the potential risk posed to food safety, environmental and public health. Key messages The increasing prevalence of multidrug-resistant Klebsiella pneumoniae requires the need to investigate more foods and environmental samples to ensure consumer safety and public health. Public health safety requires a major knowledge of the hypothetical mechanisms and routes of transmission of multidrug-resistant Klebsiella pneumoniae.

scholarly journals Isolation of the human-associated bla CTX-M-15-harbouring Klebsiella pneumoniae ST307 from a tortoise in the UK

2020 ◽  
Vol 2 (12) ◽  
Author(s):  
Geoffrey Foster ◽  
Manal AbuOun ◽  
Romain Pizzi ◽  
Bryn Tennant ◽  
Margaret McCall ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Type Species ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Public Health Concern ◽  
Emerging Pathogen ◽  
Content Type ◽  
Link Type ◽  
The Uk

The ST307 multidrug-resistant CTX-M-15-producing Klebsiella pneumoniae is an emerging pathogen, which has become disseminated worldwide in humans but is rarely reported from other reservoirs. We report the first isolation of K. pneumoniae from an animal in Europe and also from a reptile, a captive tortoise, whose death it probably caused. Detection of this clone from an animal adds to evidence of niche expansion in non-human environments, where it may amplify, recycle and become of greater public health concern.

scholarly journals Genomic diversity of antimicrobial resistance in non-typhoidal Salmonella in Victoria, Australia

2021 ◽  
Vol 7 (12) ◽  
Author(s):  
Cheryll M. Sia ◽  
Sarah L. Baines ◽  
Mary Valcanis ◽  
Darren Y. J. Lee ◽  
Anders Gonçalves da Silva ◽  
...  
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
In Silico ◽  
Multidrug Resistant ◽  
Genomic Diversity ◽  
Genomic Context ◽  
Predictive Values ◽  
Content Type ◽  
Phenotypic Resistance ◽  
Phenotypic Susceptibility

Non-typhoidal Salmonella (NTS) is the second most common cause of foodborne bacterial gastroenteritis in Australia with antimicrobial resistance (AMR) increasing in recent years. Whole-genome sequencing (WGS) provides opportunities for in silico detection of AMR determinants. The objectives of this study were two-fold: (1) establish the utility of WGS analyses for inferring phenotypic resistance in NTS, and (2) explore clinically relevant genotypic AMR profiles to third generation cephalosporins (3GC) in NTS lineages. The concordance of 2490 NTS isolates with matched WGS and phenotypic susceptibility data against 13 clinically relevant antimicrobials was explored. In silico serovar prediction and typing was performed on assembled reads and interrogated for known AMR determinants. The surrounding genomic context, plasmid determinants and co-occurring AMR patterns were further investigated for multidrug resistant serovars harbouring bla CMY-2, bla CTX-M-55 or bla CTX-M-65. Our data demonstrated a high correlation between WGS and phenotypic susceptibility testing. Phenotypic-genotypic concordance was observed between 2440/2490 (98.0 %) isolates, with overall sensitivity and specificity rates >98 % and positive and negative predictive values >97 %. The most common AMR determinants were bla TEM-1, sul2, tet(A), strA-strB and floR. Phenotypic resistance to cefotaxime and azithromycin was low and observed in 6.2 % (151/2486) and 0.9 % (16/1834) of the isolates, respectively. Several multi-drug resistant NTS lineages were resistant to 3GC due to different genetic mechanisms including bla CMY-2, bla CTX-M-55 or bla CTX-M-65. This study shows WGS can enhance existing AMR surveillance in NTS datasets routinely produced in public health laboratories to identify emerging AMR in NTS. These approaches will be critical for developing capacity to detect emerging public health threats such as resistance to 3GC.

scholarly journals Complete Genome Sequence of a Novel Multidrug-Resistant Klebsiella pneumoniae Phage, vB_Kpn_IME260

2017 ◽  
Vol 5 (19) ◽  
Author(s):  
Shaozhen Xing ◽  
Xiangchun Pan ◽  
Qiang Sun ◽  
Guangqian Pei ◽  
Xiaoping An ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Phage Therapy ◽  
Bacterial Pathogen ◽  
Genomic Data ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Drug Resistant Bacteria

ABSTRACT Klebsiella pneumoniae is the most common clinically important opportunistic bacterial pathogen and its infection is often iatrogenic. Its drug resistance poses a grave threat to public health. The genomic data reported here comprise an important resource for research on phage therapy in the control of drug-resistant bacteria.

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