scholarly journals Convergence of virulence and multidrug resistance in a single plasmid vector in multidrug-resistant Klebsiella pneumoniae ST15

2018 ◽  
Author(s):  
Margaret M. C. Lam ◽  
Kelly L. Wyres ◽  
Ryan R. Wick ◽  
Louise M. Judd ◽  
Aasmund Fostervold ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Klebsiella Pneumoniae ◽  
Treatment Options ◽  
Plasmid Vector ◽  
Multidrug Resistant ◽  
Virulence Plasmid ◽  
Genetic Determinants ◽  
Oxford Nanopore ◽  
Invasive Infections ◽  
Rapid Emergence

SYNOPSISBackgroundMultidrug resistance (MDR) and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options.ObjectivesTo characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15.MethodsThe complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing.ResultsBoth isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc) fused with sequences typical of IncFIIK conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene blaCTX-M-15 and eight other AMR genes (blaTEM, aac3’-IIa, aph3’-Ia, dfrA1, satA2, blaSHV, sul1, aadA1). The other carried remnants of these elements encoding blaTEM and aac3’-IIa, and blaCTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania.ConclusionsThe presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.

scholarly journals Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones

2021 ◽  
Author(s):  
Mattia Palmieri ◽  
Kelly L. Wyres ◽  
Caroline Mirande ◽  
Zhao Qiang ◽  
Ye Liyan ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Type Species ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Virulence Plasmid ◽  
Content Type ◽  
Origin And Evolution ◽  
Link Type ◽  
Beijing China

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

scholarly journals Inhibitors of Antibiotic Efflux in Resistant Enterobacter aerogenes and Klebsiella pneumoniae Strains

2004 ◽  
Vol 48 (3) ◽  
pp. 1043-1046 ◽  
Author(s):  
Jacqueline Chevalier ◽  
Jérôme Bredin ◽  
Abdallah Mahamoud ◽  
Monique Malléa ◽  
Jacques Barbe ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Klebsiella Pneumoniae ◽  
Efflux Pump ◽  
Enterobacter Aerogenes ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Phenotype ◽  
Pump Mechanism ◽  
Energy Dependent ◽  
Antibiotic Efflux

ABSTRACT In Enterobacter aerogenes and Klebsiella pneumoniae, efflux provides efficient extrusion of antibiotics and contributes to the multidrug resistance phenotype. One of the alkoxyquinoline derivatives studied here, 2,8-dimethyl-4-(2′-pyrrolidinoethyl)-oxyquinoline, restores noticeable drug susceptibility to resistant clinical strains. Analyses of energy-dependent chloramphenicol efflux indicate that this compound inhibits the efflux pump mechanism and improves the activity of structurally unrelated antibiotics on multidrug-resistant E. aerogenes and K. pneumoniae isolates.

scholarly journals A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001-2015: Introduction and spread of ESBL facilitated by CG15 and CG307

2021 ◽  
Author(s):  
Aasmund Fostervold ◽  
Marit A.K. Hetland ◽  
Ragna-Johanne Bakksjo ◽  
Eva Bernhoff ◽  
Kathryn Holt ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Sensu Stricto ◽  
Whole Genome Sequence ◽  
Surveillance Program ◽  
Esbl Production ◽  
Resistance Determinants ◽  
Oxford Nanopore ◽  
Genomic Study ◽  
Plasmid Replicons

Objective: We have used the nationwide Norwegian surveillance program on resistant microbes in humans (NORM) to address longitudinal changes in the population structure K. pneumoniae isolates during 2001-15, encompassing the emergence and spread of ESBL-producing Enterobacterales (ESBL-E) in Norway. Material and methods: Among blood (n= 6124) and urinary tract (n=5496) surveillance isolates from 2001-15, we used Illumina technology to whole genome sequence 201 ESBL-producing isolates from blood (n=130) and urine (n=71), and 667 non-ESBL isolates from blood. Complete genomes for four isolates were resolved with Oxford Nanopore sequencing. Results: In a highly diverse collection, Klebsiella variicola ssp. variicola caused a quarter of Klebsiella pneumoniae species complex bacteraemias. ESBL-production was limited to K. pneumoniae sensu stricto (98.5 %). A diverse ESBL population of 57 clonal groups (CGs) were dominated by multidrug resistant CG307 (17%), CG15 (12%), CG70 (6%), CG258 (5%) and CG45 (5%) carrying blaCTX-M-15. Yersiniabactin was significantly more common in ESBL-positive (37.8%) compared to non-ESBL K. pneumoniae sensu stricto isolates (12.7%), indicating convergence of virulence and resistance determinants. Moreover, we found a significant lower prevalence of yersinabactin (3.0 %, 37.8 % and 17.3 %), IncFIB (58.7 %, 87.9 % and 79.4 %) and IncFII plasmid replicons (40.5 %, 82.8 % and 54.2%) in K. variicola ssp. variicola compared to ESBL- and non-ESBL K. pneumoniae sensu stricto, respectively. Conclusion: The increase in Norwegian KpSC ESBLs during 2010-15 was driven by blaCTX-M-15 carrying CG307 and CG15. K. variicola ssp. variicola was a frequent cause of invasive KpSC infection, but rarely carried ESBL.

scholarly journals EVALUATION OF EFFLUX PUMP ACTIVITY AND BIOFILM FORMATION IN MULTIDRUG RESISTANT KLEBSIELLA PNEUMONIAE ISOLATES IN TANTA, EGYPT

2021 ◽  
Vol 12 (3) ◽  
pp. 1-5
Author(s):  
Tarek El-Said El-Banna ◽  
Fatma Ibrahim Sonbol ◽  
Heba M El-Dawy ◽  
Lamiaa A Al-Madboly
Keyword(s):  
Drug Resistance ◽  
Klebsiella Pneumoniae ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
High Morbidity ◽  
Biochemical Tests ◽  
Antibiotic Resistance Profile ◽  
Pump Activity

Nosocomial and community acquired infections that caused by multidrug-resistant (MDR) Klebsiella pneumoniae isolates are widespread recently resulting in high morbidity and mortality due to limited number of treatment options with effective antibiotics. The aim of this study is to evaluate the antibiotic resistance profile, biofilm formation and efflux pump activity of MDR K. pneumoniae isolates collected from different hospitals in Tanta, Egypt. A total of 70 K. pneumoniae isolates characterized by standard biochemical tests and confirmed by MALDI-TOF/MS were screened for antibiotic susceptibility, efflux pump activity and biofilm formation. Isolates displayed high resistance to penicillins, cephalosporins, trimethoprim-sulfamethoxazole and the majority of tested fluoro/-quinolones and decreased resistance to imipenem, amikacin, chloramphenicol, tigecycline and colistin. Out of 70 K. pneumoniae isolates, 2 isolates exhibited Pan Drug-Resistance (PDR) profile while 57 (81.4%) and 11 (15.7%) exhibited MDR and Extensively drug-resistance (XDR) profiles, respectively. Sixty-four (91.4%) isolates exhibited efflux pump activity while all tested isolates had the ability to form biofilm with varied degrees as 40 (57.1%), 26 (37.1%), and 4 (5.7%) isolates were strong, moderate and weak biofilm producers, respectively. Also, a strong relation between efflux pump activity and biofilm formation per isolate was detected. In conclusion, Multidrug resistance, biofilm formation and efflux pump capabilities in K. pneumoniae have serious public health implications in the management and control of infections caused by this bacterium. Therefore, a multifaceted approach and precise planning are recommended in controlling these infections

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 Treatment Options for Colistin Resistant Klebsiella pneumoniae: Present and Future

2019 ◽  
Vol 8 (7) ◽  
pp. 934 ◽  
Author(s):  
Petrosillo ◽  
Taglietti ◽  
Granata
Keyword(s):  
Monoclonal Antibodies ◽  
Side Effects ◽  
Mortality Rate ◽  
Klebsiella Pneumoniae ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Limited Range ◽  
Therapeutic Strategies ◽  
Colistin Resistance ◽  
Carbapenem Resistant

Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.

scholarly journals Innate Host Defense against Klebsiella pneumoniae and the Outlook for Development of Immunotherapies

2021 ◽  
pp. 1-15
Author(s):  
Clement Opoku-Temeng ◽  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Frank R. DeLeo
Keyword(s):  
Klebsiella Pneumoniae ◽  
Host Defense ◽  
Severe Disease ◽  
Treatment Options ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Severe Illness ◽  
Preventative Measures ◽  
Number Of Treatment ◽  
Healthcare Associated

<i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) is a Gram-negative commensal bacterium and opportunistic pathogen. In healthy individuals, the innate immune system is adept at protecting against <i>K. pneumoniae</i> infection. Notably, the serum complement system and phagocytic leukocytes (e.g., neutrophils) are highly effective at eliminating <i>K. pneumoniae</i> and thereby preventing severe disease. On the other hand, the microbe is a major cause of healthcare-associated infections, especially in individuals with underlying susceptibility factors, such as pre-existing severe illness or immune suppression. The burden of <i>K. pneumoniae</i> infections in hospitals is compounded by antibiotic resistance. Treatment of these infections is often difficult largely because the microbes are usually resistant to multiple antibiotics (multidrug resistant [MDR]). There are a limited number of treatment options for these infections and new therapies, and preventative measures are needed. Here, we review host defense against <i>K. pneumoniae</i> and discuss recent therapeutic measures and vaccine approaches directed to treat and prevent severe disease caused by MDR <i>K. pneumoniae</i>.

scholarly journals Integrons and Transposons on the Salmonellaenterica Serovar Typhimurium Virulence Plasmid

2005 ◽  
Vol 49 (3) ◽  
pp. 1194-1197 ◽  
Author(s):  
Laura Villa ◽  
Alessandra Carattoli
Keyword(s):  
Multidrug Resistance ◽  
Resistance Gene ◽  
Virulence Genes ◽  
Multidrug Resistant ◽  
Virulence Plasmid ◽  
Virulence Determinants ◽  
Plasmid Evolution ◽  
Class 1 Integrons ◽  
Serovar Typhimurium ◽  
Class 1

ABSTRACT A virulence plasmid was identified in a multidrug-resistant Salmonella enterica serotype Typhimurium strain carrying the spvC, rck, and pefA virulence genes and two class 1 integrons linked to the Tn21 and Tn1696 transposons. A novel trimethoprim resistance gene, designated dfrA23, was also identified within the integron region. The association of multidrug resistance and virulence determinants represents an interesting example of virulence plasmid evolution.

scholarly journals Occurrence and characterization of hyperviscous K1 and K2 serotype in Klebsiella pneumoniael

2018 ◽  
Vol 10 (03) ◽  
pp. 283-288 ◽  
Author(s):  
Poothakuzhiyil Remya ◽  
Mariappan Shanthi ◽  
Uma Sekar
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Clinical Samples ◽  
Beta Lactamases ◽  
New Variant ◽  
Invasive Infections ◽  
Extended Spectrum Beta Lactamases ◽  
Encoding Genes ◽  
Serotype K2

ABSTRACT BACKGROUND: Klebsiella pneumoniae causes both nosocomial and community-associated infections. Hypervirulent K. pneumoniae (hvKP), new variant of K. pneumoniae, can cause invasive infections in young healthy individuals as well as in the immunocompromised population. Hypervirulent strains frequently belong to capsular serotypes K1 or K2. Emergence of antimicrobial resistance in hvKP is a cause for concern. AIM AND OBJECTIVE: The present study was done to detect the K1 and K2 serotypes among clinical isolates of K. pneumoniae, spectrum of infections caused by them and presence of common beta-lactamases encoding genes in them. MATERIALS AND METHODS: A total of 370 isolates of K. pneumoniae, isolated from various clinical samples over a period of 1 year was included in this study. Antibiotic susceptibility testing to various classes of antimicrobials was done as per Clinical and Laboratory Standard Institute guidelines. The presence of K2A (specific to serotype K2), magA (specific to serotype K1), and rmpA genes was detected by multiplex polymerase chain reaction (PCR). Extended-spectrum beta-lactamases (TEM, SHV, and CTX-M), plasmid-mediated AmpCs (MOX, CIT, DHA, ACC, EBC, and FOX), and carbapenemase genes (IMP, VIM, NDM, KPC, and OXA-48) were also determined by PCR. RESULTS: Among the 370 isolates, 8 harbored K2A gene and one harbored magA. rmpA gene was detected in three isolates along with K1 or K2 serotypes. Seven K2A-positive isolates were resistant to one or more classes of antimicrobials. The studied ESBL genes were present in four isolates. Two isolates harbored carbapenemase genes (NDM-1, OXA-48) along with ESBLs. Conclusions: K2 serotype is more prevalent among hvKP isolates. They can harbor ESBLs and Carbapenemase genes. K1 serotype is rather uncommon in K. pneumoniae. Acquisition of multidrug-resistant genes by these strains adds to their virulence and limits the treatment options.

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