scholarly journals Comparative Genomics Reveals a Well-Conserved Intrinsic Resistome in the Emerging Multidrug-Resistant Pathogen Cupriavidus gilardii

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Cristian Ruiz ◽  
Ashley McCarley ◽  
Manuel Luis Espejo ◽  
Kerry K. Cooper ◽  
Dana E. Harmon
Keyword(s):  
Antibiotic Resistance ◽  
Comparative Genomics ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Antibiotics Resistance ◽  
Whole Genome ◽  
Intrinsic Resistance ◽  
Content Type

ABSTRACT The Gram-negative bacterium Cupriavidus gilardii is an emerging multidrug-resistant pathogen found in many environments. However, little is known about this species or its antibiotic resistance mechanisms. We used biochemical tests, antibiotic susceptibility experiments, and whole-genome sequencing to characterize an environmental C. gilardii isolate. Like clinical isolates, this isolate was resistant to meropenem, gentamicin, and other antibiotics. Resistance to these antibiotics appeared to be related to the large number of intrinsic antibiotic resistance genes found in this isolate. As determined by comparative genomics, this resistome was also well conserved in the only two other C. gilardii strains sequenced to date. The intrinsic resistome of C. gilardii did not include the colistin resistance gene mcr-5, which was in a transposon present only in one strain. The intrinsic resistome of C. gilardii was comprised of (i) many multidrug efflux pumps, such as a homolog of the Pseudomonas aeruginosa MexAB-OprM pump that may be involved in resistance to meropenem, other β-lactams, and aminoglycosides; (ii) a novel β-lactamase (OXA-837) that decreases susceptibility to ampicillin but not to other β-lactams tested; (iii) a new aminoglycoside 3-N-acetyltransferase [AAC(3)-IVb, AacC10] that decreases susceptibility to gentamicin and tobramycin; and (iv) a novel partially conserved aminoglycoside 3ʺ-adenylyltransferase [ANT(3ʺ)-Ib, AadA32] that decreases susceptibility to spectinomycin and streptomycin. These findings provide the first mechanistic insight into the intrinsic resistance of C. gilardii to multiple antibiotics and its ability to become resistant to an increasing number of drugs during therapy. IMPORTANCE Cupriavidus gilardii is a bacterium that is gaining increasing attention both as an infectious agent and because of its potential use in the detoxification of toxic compounds and other biotechnological applications. In recent years, however, there has been an increasing number of reported infections, some of them fatal, caused by C. gilardii. These infections are hard to treat because this bacterium is naturally resistant to many antibiotics, including last-resort antibiotics, such as carbapenems. Moreover, this bacterium often becomes resistant to additional antibiotics during therapy. However, little is known about C. gilardii and its antibiotic resistance mechanisms. The significance of our research is in providing, for the first time, whole-genome information about the natural antibiotic resistance genes found in this bacterium and their conservation among different C. gilardii strains. This information may provide new insights into the appropriate use of antibiotics in combating infections caused by this emerging pathogen.

scholarly journals Genomic Analysis of the Multidrug-Resistant Acinetobacter baumannii Strain MDR-ZJ06 Widely Spread in China

2011 ◽  
Vol 55 (10) ◽  
pp. 4506-4512 ◽  
Author(s):  
Hua Zhou ◽  
Tongwu Zhang ◽  
Dongliang Yu ◽  
Borui Pi ◽  
Qing Yang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Resistance Island

ABSTRACTWe previously reported that the multidrug-resistant (MDR)Acinetobacter baumanniistrain MDR-ZJ06, belonging to European clone II, was widely spread in China. In this study, we report the whole-genome sequence of this clinically important strain. A 38.6-kb AbaR-type genomic resistance island (AbaR22) was identified in MDR-ZJ06. AbaR22 has a structure similar to those of the resistance islands found inA. baumanniistrains AYE and AB0057, but it contained only a few antibiotic resistance genes. The region of resistant gene accumulation as previously described was not found in AbaR22. In the chromosome of the strain MDR-ZJ06, we identified the geneblaoxa-23in a composite transposon (Tn2009). Tn2009shared the backbone with otherA. baumanniitransponsons that harborblaoxa-23, but it was bracketed by two ISAba1elements which were transcribed in the same orientation. MDR-ZJ06 also expressed thearmAgene on its plasmid pZJ06, and this gene has the same genetic environment as thearmAgene of theEnterobacteriaceae. These results suggest variability of resistance acquisition even in closely relatedA. baumanniistrains.

scholarly journals Environmental Spread of New Delhi Metallo-β-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh

2017 ◽  
Vol 83 (15) ◽  
Author(s):  
Mohammad Aminul Islam ◽  
Moydul Islam ◽  
Rashedul Hasan ◽  
M. Iqbal Hossain ◽  
Ashikun Nabi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Tap Water ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
New Delhi ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
Wastewater Samples

ABSTRACT Resistance to carbapenem antibiotics through the production of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community. IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

scholarly journals CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis

mSphere ◽  
2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Valerie J. Price ◽  
Wenwen Huo ◽  
Ardalan Sharifi ◽  
Kelli L. Palmer
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Enterococcus Faecalis ◽  
Resistance Genes ◽  
Treatment Options ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Content Type ◽  
New Genes ◽  
Restriction Modification

ABSTRACT Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics. Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.

scholarly journals Comparative Genomics of Klebsiella pneumoniae Strains with Different Antibiotic Resistance Profiles

2011 ◽  
Vol 55 (9) ◽  
pp. 4267-4276 ◽  
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.

scholarly journals Whole-Genome Sequence of ablaOXA-48-Harboring Raoultella ornithinolytica Clinical Isolate from Lebanon

2016 ◽  
Vol 60 (4) ◽  
pp. 2548-2550 ◽  
Author(s):  
Charbel Al-Bayssari ◽  
Abiola Olumuyiwa Olaitan ◽  
Thongpan Leangapichart ◽  
Liliane Okdah ◽  
Fouad Dabboussi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Isolate ◽  
Genome Sequence ◽  
Resistance Genes ◽  
Molecular Mechanisms ◽  
Antibiotic Resistance Genes ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Genetic Organization

ABSTRACTWe analyzed the whole-genome sequence of ablaOXA-48-harboringRaoultella ornithinolyticaclinical isolate from a patient in Lebanon. The size of theRaoultella ornithinolyticaCMUL058 genome was 5,622,862 bp, with a G+C content of 55.7%. We deciphered all the molecular mechanisms of antibiotic resistance, and we compared our genome to other availableR. ornithinolyticagenomes in GenBank. The resistome consisted of 9 antibiotic resistance genes, including a plasmidicblaOXA-48gene whose genetic organization is also described.

scholarly journals Combining Functional Genomics and Whole-Genome Sequencing to Detect Antibiotic Resistance Genes in Bacterial Strains Co-Occurring Simultaneously in a Brazilian Hospital

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 419
Author(s):  
Tiago Cabral Borelli ◽  
Gabriel Lencioni Lovate ◽  
Ana Flavia Tonelli Scaranello ◽  
Lucas Ferreira Ribeiro ◽  
Livia Zaramela ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Functional Genomics ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Resistant Bacteria ◽  
Whole Genome ◽  
Beta Lactamase ◽  
Bacterial Strains

(1) Background: The rise of multi-antibiotic resistant bacteria represents an emergent threat to human health. Here, we investigate antibiotic resistance mechanisms in bacteria of several species isolated from an intensive care unit in Brazil. (2) Methods: We used whole-genome analysis to identify antibiotic resistance genes (ARGs) and plasmids in 34 strains of Gram-negative and Gram-positive bacteria, providing the first genomic description of Morganella morganii and Ralstonia mannitolilytica clinical isolates from South America. (3) Results: We identified a high abundance of beta-lactamase genes in resistant organisms, including seven extended-spectrum beta-lactamases (OXA-1, OXA-10, CTX-M-1, KPC, TEM, HYDRO, BLP) shared between organisms from different species. Additionally, we identified several ARG-carrying plasmids indicating the potential for a fast transmission of resistance mechanism between bacterial strains. Furthermore, we uncovered two pairs of (near) identical plasmids exhibiting multi-drug resistance. Finally, since many highly resistant strains carry several different ARGs, we used functional genomics to investigate which of them were indeed functional. In this sense, for three bacterial strains (Escherichia coli, Klebsiella pneumoniae, and M. morganii), we identified six beta-lactamase genes out of 15 predicted in silico as those mainly responsible for the resistance mechanisms observed, corroborating the existence of redundant resistance mechanisms in these organisms. (4) Conclusions: Systematic studies similar to the one presented here should help to prevent outbreaks of novel multidrug-resistant bacteria in healthcare facilities.

scholarly journals Whole-Genome Sequencing of a Salmonella enterica subsp. enterica Serovar Infantis Strain Isolated from Broiler Chicken in Peru

2019 ◽  
Vol 8 (43) ◽  
Author(s):  
Katherine Vallejos-Sánchez ◽  
Luis Tataje-Lavanda ◽  
Doris Villanueva-Pérez ◽  
Jorge Bendezú ◽  
Ángela Montalván ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Genome Sequencing ◽  
Salmonella Enterica ◽  
Genetic Information ◽  
Broiler Chicken ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type

This report shows the whole-genome sequence of the multidrug-resistant Salmonella enterica subsp. enterica serovar Infantis strain FARPER-219. Antibiotic resistance genes are found mainly in the plasmid. Our findings show important genetic information that provides an understanding of the recent spread of this serotype in poultry.

scholarly journals Whole Genome Sequencing and Beta-Lactam Resistant Genes in Klebsiella pneumoniae Strains Clinically Isolated from CU Shah Hospital, Gujarat, India

2021 ◽  
Vol 14 (4) ◽  
pp. 1847-1854
Author(s):  
Vaibhavi Patel
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Virulence Gene ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Beta Lactam ◽  
Resistance Profile ◽  
Antibiotic Resistance Profile

A simple explanation for antimicrobial-resistant opportunistic infections in immunocompromised patients is Klebsiella pneumoniae which gradually being associated in insidious infections globally with high mortality rate. Eight hundred fifty-six antibiotic resistant K. pneumoniae isolates were collected over 3 years period (from different wards and different specimens) from the Microbiology department of C.U. Shah hospital, whose AST checked by Kirby Bauer disk diffusion method. To study AMR genes, virulome, interference of virulence gene with resistance gene, phylogenomic; 6 clinical isolates were proceeded for whole genome sequencing and bio informatics analysis. Klebsiella pneumoniae is a multidrug-resistant (MDR) opportunistic and one of delegate of ESKAPE pathogens groups. This pathogen causes nosocomial infections, urinary tract infections, liver abscesses, wound infections, meningitis. These strains obtain a multidrug resistant phenotype by way of horizontal transfer of ARG transported by either transposons or plasmids. This transfer is generally facilitated by Integrons. In this study antibiotic resistance profile and antibiotic resistance genes analysis as well as virulence gene of K. pneumoniae strains were investigated. The study was carried out using 853 clinical isolates collected during 3 years from C.U. Shah hospital of Surendranagar. Antibiotic resistance profile test was carried out by the VITEK 2 against 21 antibiotics. Out of that 6 samples were proceed for DNA extraction, WGS illumina sequencer and analysis of those raw sequences by TORMES pipeline. In this study antibiotic resistance profile included 13 beta lactam antibiotics which classified under 3 class (Penicillin, Cephalosporin, Carbapenem) of beta lactam and in AMR gene study got total 15 different ESBL resistance genes from 6 different klebsiella pneumoniae strain. All these genes detected with more than 90% identity by CARD. (TORMES Pipeline) CTX-M-15, NDM-5, OKP-B-6, PDC-2, OXA-1, OXA-181, OXA-362, OXA-50, OXA-9, SHV-1, SHV-11, SHV-187, TEM-1, TEM-150. In this study, we’ve analyzed the pattern of antibiotic resistance pattern as a phenotypic characteristic and antibiotic resistance genes as genotypic characteristic and co related the results. As multidrug resistance is a worrying matter, constant observation and regular clinical recognition of resistant bacteria are essential to avoid terrible public health incidents. So, our data should be inferred as a warning for need for prevention and control of the MDR K. pneumoniae in hospital settings.

Antibiotic resistance genes and virulence factors in Enterococcus faecium and Enterococcus faecalis from diseased farm animals: pigs, cattle and poultry

2012 ◽  
Vol 15 (3) ◽  
pp. 431-438 ◽  
Author(s):  
V. Sˇ Eputiene˙ ◽  
A. Bogdaite˙ ◽  
M. Ruzˇauskas ◽  
E. Suzˇiede˙Liene˙
Keyword(s):  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Farm Animals ◽  
Antibiotics Resistance ◽  
Erythromycin Resistance ◽  
Aminoglycoside Resistance ◽  
Chloramphenicol Resistance

AbstractEighty enterococcal isolates (E. faecium, n=38,E. faecalis, n=42) from diseased farm animals (swine, cattle, poultry) in Lithuania have been studied for the prevalence of antibiotic resistance and for resistance and virulence genetic determinants. 86% ofE. faeciumand 71% ofE. faecalisisolates were multidrug resistant (resistant to three or more unrelated antibiotics). Resistance to aminoglycosides, tetracycline and erythromycin was found most frequently in both species (61%, 69%) and was linked toaph(3’)-IIIa,aac(6’)-Ie-aph(2”)-Ia,ant(6)-Ia (aminoglycoside resistance),tetM,tetL(tetracycline resistance),ermA,ermB(erythromycin resistance) gene combinations, which were supplemented with chloramphenicol resistance genescatA7,catA8(E. faecalis) andcatA9(E. faecium). AllE. faecalisisolates harboured genes coding for virulence factorsagg,esp,fsr gelEalone or in combinations with the high prevalence ofespgene in isolates from cattle (63%) and pigs (79%). The origin- dependent incidence ofagggene variantsprgBandasp1was observed. The results indicate the existence of a large pool of potentially virulent and multidrug resistantE. faecalisin diseased farm animals posing risk to humans.

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