Beta-lactamase and integron-associated antibiotic resistance genes of Klebsiella pneumoniae isolated from Tilapia fishes (Oreochromis niloticus)

Abstract Background The spread of antibiotic resistance has become one of the most urgent threats to global health, which is estimated to cause 700,000 deaths each year globally. Its surrogates, antibiotic resistance genes (ARGs), are highly transmittable between food, water, animal, and human to mitigate the efficacy of antibiotics. Accurately identifying ARGs is thus an indispensable step to understanding the ecology, and transmission of ARGs between environmental and human-associated reservoirs. Unfortunately, the previous computational methods for identifying ARGs are mostly based on sequence alignment, which cannot identify novel ARGs, and their applications are limited by currently incomplete knowledge about ARGs. Results Here, we propose an end-to-end Hierarchical Multi-task Deep learning framework for ARG annotation (HMD-ARG). Taking raw sequence encoding as input, HMD-ARG can identify, without querying against existing sequence databases, multiple ARG properties simultaneously, including if the input protein sequence is an ARG, and if so, what antibiotic family it is resistant to, what resistant mechanism the ARG takes, and if the ARG is an intrinsic one or acquired one. In addition, if the predicted antibiotic family is beta-lactamase, HMD-ARG further predicts the subclass of beta-lactamase that the ARG is resistant to. Comprehensive experiments, including cross-fold validation, third-party dataset validation in human gut microbiota, wet-experimental functional validation, and structural investigation of predicted conserved sites, demonstrate not only the superior performance of our method over the state-of-art methods, but also the effectiveness and robustness of the proposed method. Conclusions We propose a hierarchical multi-task method, HMD-ARG, which is based on deep learning and can provide detailed annotations of ARGs from three important aspects: resistant antibiotic class, resistant mechanism, and gene mobility. We believe that HMD-ARG can serve as a powerful tool to identify antibiotic resistance genes and, therefore mitigate their global threat. Our method and the constructed database are available at http://www.cbrc.kaust.edu.sa/HMDARG/.

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Comparative Genomics of Klebsiella pneumoniae Strains with Different Antibiotic Resistance Profiles

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00052-11 ◽

2011 ◽

Vol 55 (9) ◽

pp. 4267-4276 ◽

Cited By ~ 48

Author(s):

Vinod Kumar ◽

Peng Sun ◽

Jessica Vamathevan ◽

Yong Li ◽

Karen Ingraham ◽

...

Keyword(s):

Antibiotic Resistance ◽

Multidrug Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Susceptible Strain ◽

Clinical Isolates ◽

Whole Genome ◽

Content Type ◽

Extended Spectrum

ABSTRACTThere is a global emergence of multidrug-resistant (MDR) strains ofKlebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. While the epidemiology ofK. pneumoniaestrains and occurrences of specific antibiotic resistance genes, such as plasmid-borne extended-spectrum β-lactamases (ESBLs), have been extensively studied, only four complete genomes ofK. pneumoniaeare available. To better understand the multidrug resistance factors inK. pneumoniae, we determined by pyrosequencing the nearly complete genome DNA sequences of two strains with disparate antibiotic resistance profiles, broadly drug-susceptible strain JH1 and strain 1162281, which is resistant to multiple clinically used antibiotics, including extended-spectrum β-lactams, fluoroquinolones, aminoglycosides, trimethoprim, and sulfamethoxazoles. Comparative genomic analysis of JH1, 1162281, and other publishedK. pneumoniaegenomes revealed a core set of 3,631 conserved orthologous proteins, which were used for reconstruction of whole-genome phylogenetic trees. The close evolutionary relationship between JH1 and 1162281 relative to otherK. pneumoniaestrains suggests that a large component of the genetic and phenotypic diversity of clinical isolates is due to horizontal gene transfer. Using curated lists of over 400 antibiotic resistance genes, we identified all of the elements that differentiated the antibiotic profile of MDR strain 1162281 from that of susceptible strain JH1, such as the presence of additional efflux pumps, ESBLs, and multiple mechanisms of fluoroquinolone resistance. Our study adds new and significant DNA sequence data onK. pneumoniaestrains and demonstrates the value of whole-genome sequencing in characterizing multidrug resistance in clinical isolates.

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Cohorting KPC+ Klebsiella pneumoniae (KPC-Kp)–positive patients: A genomic exposé of cross-colonization hazards in a long-term acute-care hospital (LTACH)

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.261 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1162-1168

Author(s):

Shawn E. Hawken ◽

Mary K. Hayden ◽

Karen Lolans ◽

Rachel D. Yelin ◽

Robert A. Weinstein ◽

...

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Acute Care ◽

Resistance Genes ◽

Acute Care Hospital ◽

Antibiotic Resistance Genes ◽

Care Hospital ◽

Cross Transmission ◽

The Impact

AbstractObjective:Cohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) protects uncolonized patients from acquiring MDROs in healthcare settings. The potential for cross transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits is often neglected. We searched for evidence of cross transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute-care hospital (LTACH), and we evaluated the impact of secondary acquisitions on resistance potential.Design:Genomic epidemiological investigation.Setting:A high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp–positive patients.Methods:Whole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross transmission between cohorted patients.Results:Secondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient’s isolate than to their own admission isolate. Of these 19 cases, 14 showed strong genomic evidence for cross transmission (<10 single nucleotide variants or SNVs), and most of these patients occupied shared cohort floors (12 patients) or rooms (4 patients) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates.Conclusions:Acquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and they indicate the need for future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.

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New antibiotic resistance genes associated with CTX-M plasmids from uropathogenic Nigerian Klebsiella pneumoniae

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkl370 ◽

2006 ◽

Vol 58 (5) ◽

pp. 1048-1053 ◽

Cited By ~ 41

Author(s):

O. O. Soge ◽

B. A. Adeniyi ◽

M. C. Roberts

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Antibiotic Resistance Genes

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Exploring divergent antibiotic resistance genes in ancient metagenomes and discovery of a novel beta-lactamase family

Environmental Microbiology Reports ◽

10.1111/1758-2229.12453 ◽

2016 ◽

Vol 8 (5) ◽

pp. 886-895 ◽

Cited By ~ 11

Author(s):

Nicolás Rascovan ◽

Amar Telke ◽

Didier Raoult ◽

Jean Marc Rolain ◽

Christelle Desnues

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Beta Lactamase

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Investigation of the antibiotic resistance and biofilm formation of Staphylococcus aureus strains isolated from gangrenous mastitis of ewes

Acta Veterinaria Hungarica ◽

10.1556/avet.2012.016 ◽

2012 ◽

Vol 60 (2) ◽

pp. 189-197 ◽

Cited By ~ 7

Author(s):

Osman Tel ◽

Özkan Aslantaş ◽

Oktay Keskin ◽

Ebru Yilmaz ◽

Cemil Demir

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Virulence Factor ◽

Resistance Genes ◽

Biofilm Formation ◽

Antibiotic Resistance Genes ◽

Penicillin G ◽

Beta Lactamase ◽

Potential Virulence Factor ◽

Amoxicillin Clavulanic Acid

In this study,Staphylococcus aureusstrains (n = 110) isolated from seven ewe flocks in Sanliurfa, Turkey were screened for antibiotic resistance and biofilmforming ability as well as for genes associated with antibiotic resistance and biofilm-forming ability. All isolates were found to be susceptible to oxacillin, gentamicin, clindamycin, cefoxitin, tetracycline, vancomycin, amoxicillin-clavulanic acid, ciprofloxacin and sulphamethoxazole-trimethoprim. The percent proportions of strains resistant to penicillin G, ampicillin and erythromycin were 27.2% (n = 30), 25.4% (n = 28) and 6.3% (n = 7), respectively. Regarding the antibiotic resistance genes, 32 (29%) isolates carried theblaZ and 8 (7.2%) theermC gene. Other resistance genes were not detected in the isolates. All isolates showed biofilm-forming ability on Congo red agar (CRA), while 108 (98.18%) and 101 (91.81%) of them were identified as biofilm producers by the use of standard tube (ST) and microplate (MP) methods, respectively. All isolates carried theicaA andicaD genes but none of them harboured thebapgene. The results demonstrated thatS. aureusisolates from gangrenous mastitis were mainly resistant to penicillins (which are susceptible to the staphylococcal beta-lactamase enzyme), and less frequently to erythromycin. Furthermore, all of theS. aureusisolates produced biofilm which was considered a potential virulence factor in the pathogenesis of staphylococcal mastitis.

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Differences in Resolution of mwr-Containing Plasmid Dimers Mediated by the Klebsiella pneumoniae and Escherichia coli XerC Recombinases: Potential Implications in Dissemination of Antibiotic Resistance Genes

Journal of Bacteriology ◽

10.1128/jb.188.8.2812-2820.2006 ◽

2006 ◽

Vol 188 (8) ◽

pp. 2812-2820 ◽

Cited By ~ 15

Author(s):

Duyen Bui ◽

Judianne Ramiscal ◽

Sonia Trigueros ◽

Jason S. Newmark ◽

Albert Do ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Recombination Site ◽

Lower Efficiency ◽

E Coli ◽

N Terminus ◽

Α Helix

ABSTRACT Xer-mediated dimer resolution at the mwr site of the multiresistance plasmid pJHCMW1 is osmoregulated in Escherichia coli containing either the Escherichia coli Xer recombination machinery or Xer recombination elements from K. pneumoniae. In the presence of K. pneumoniae XerC (XerCKp), the efficiency of recombination is lower than that in the presence of the E. coli XerC (XerCEc) and the level of dimer resolution is insufficient to stabilize the plasmid, even at low osmolarity. This lower efficiency of recombination at mwr is observed in the presence of E. coli or K. pneumoniae XerD proteins. Mutagenesis experiments identified a region near the N terminus of XerCKp responsible for the lower level of recombination catalyzed by XerCKp at mwr. This region encompasses the second half of the predicted α-helix B and the beginning of the predicted α-helix C. The efficiencies of recombination at other sites such as dif or cer in the presence of XerCKp or XerCEc are comparable. Therefore, XerCKp is an active recombinase whose action is impaired on the mwr recombination site. This characteristic may result in restriction of the host range of plasmids carrying this site, a phenomenon that may have important implications in the dissemination of antibiotic resistance genes.

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Multidrug-Resistant Klebsiella pneumoniae Isolated from Farm Environments and Retail Products in Oklahoma

Journal of Food Protection ◽

10.4315/0362-028x-68.10.2022 ◽

2005 ◽

Vol 68 (10) ◽

pp. 2022-2029 ◽

Cited By ~ 46

Author(s):

SHIN-HEE KIM ◽

CHENG-I WEI ◽

YWH-MIN TZOU ◽

HAEJUNG AN

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Meat Products ◽

Antibiotic Resistance Genes ◽

Enteric Bacteria ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Gene Encoding ◽

Class 1

Multidrug-resistant enteric bacteria were isolated from turkey, cattle, and chicken farms and retail meat products in Oklahoma. Among the isolated species, multidrug-resistant Klebsiella pneumoniae was prevalently isolated from most of the collected samples. Therefore, a total of 132 isolates of K. pneumoniae were characterized to understand their potential roles in the dissemination of antibiotic-resistance genes in the food chains. Multidrug-resistant K. pneumoniae was most frequently recovered from a turkey farm and ground turkey products among the tested samples. All isolates were resistant to ampicillin, tetracycline, streptomycin, gentamycin, and kanamycin. Class 1 integrons located in plasmids were identified as a common carrier of the aadA1 gene, encoding resistance to streptomycin and spectinomycin. Production of β-lactamase in the K. pneumoniae isolates played a major role in the resistance to β-lactam agents. Most isolates (96%) possessed blaSHV-1. Five strains were able to express both SHV-11 (pI 6.2) and TEM-1 (pI 5.2) β-lactamase. Transfer of these antibiotic-resistance genes to Escherichia coli was demonstrated by transconjugation. The bacterial genomic DNA restriction patterns by pulsed-field gel electrophoresis showed that the same clones of multidrug-resistant K. pneumoniae remained in feathers, feed, feces, and drinking water in turkey environments, indicating the possible dissemination of antibiotic-resistance genes in the ecosystem and cross-contamination of antibiotic-resistant bacteria during processing and distribution of products.

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