Pandrug-resistant Acinetobacter baumannii from different clones and regions in Mexico have a similar plasmid carrying the bla OXA-72 gene

Background Multidrug-resistant Acinetobacter baumannii is a common hospital-acquired pathogen. The increase in antibiotic resistance is commonly due to the acquisition of mobile genetic elements carrying antibiotic resistance genes. To comprehend this, we analyzed the resistome and virulome of Mexican A. baumannii multidrug-resistant isolates. Methods Six clinical strains of A. baumannii from three Mexican hospitals were sequenced using the Illumina platform, the genomes were assembled with SPAdes and annotated with Prokka. Plasmid SPAdes and MobRecon were used to identify the potential plasmid sequences. Sequence Type (ST) assignation under the MLST Oxford scheme was performed using the PubMLST database. Homologous gene search for known virulent factors was performed using the virulence factor database VFDB and an in silico prediction of the resistome was conducted via the ResFinder databases. Results The six strains studied belong to different STs and clonal complexes (CC): two strains were ST208 and one was ST369; these two STs belong to the same lineage CC92, which is part of the international clone (IC) 2. Another two strains were ST758 and one was ST1054, both STs belonging to the same lineage CC636, which is within IC5. The resistome analysis of the six strains identified between 7 to 14 antibiotic resistance genes to different families of drugs, including beta-lactams, aminoglycosides, fluoroquinolones and carbapenems. We detected between 1 to 4 plasmids per strain with sizes from 1,800 bp to 111,044 bp. Two strains from hospitals in Mexico City and Guadalajara had a plasmid each of 10,012 bp pAba78r and pAba79f, respectively, which contained the bla OXA-72 gene. The structure of this plasmid showed the same 13 genes in both strains, but 4 of them were inverted in one of the strains. Finally, the six strains contain 49 identical virulence genes related to immune response evasion, quorum-sensing, and secretion systems, among others. Conclusion Resistance to carbapenems due to pAba78r and pAba79f plasmids in Aba pandrug-resistant strains from different geographic areas of Mexico and different clones was detected. Our results provide further evidence that plasmids are highly relevant for the horizontal transfer of antibiotic resistance genes between different clones of A. baumannii.

[1]  S. Giono-Cerezo,et al.  Gram-negative ESKAPE bacteria bloodstream infections in patients during the COVID-19 pandemic , 2023, PeerJ.

[2]  B. Jovčić,et al.  Comparative genomics and molecular epidemiology of colistin-resistant Acinetobacter baumannii , 2022, Computational and structural biotechnology journal.

[3]  T. Nogueira,et al.  Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids , 2022, Antibiotics.

[4]  S. Castillo-Ramírez,et al.  The promiscuous and highly mobile resistome of Acinetobacter baumannii , 2022, Microbial genomics.

[5]  Israa M. S. Al-Kadmy,et al.  Multidrug-resistant Acinetobacter baumannii as an emerging concern in hospitals , 2021, Molecular Biology Reports.

[6]  S. Castillo-Ramírez,et al.  Accessory Genomic Epidemiology of Cocirculating Acinetobacter baumannii Clones , 2021, mSystems.

[7]  K. A. Noghabi,et al.  Screening of anti-Acinetobacter baumannii phytochemicals, based on the potential inhibitory effect on OmpA and OmpW functions , 2021, bioRxiv.

[8]  J. D. Di Conza,et al.  Dissemination of blaNDM–1 Gene Among Several Klebsiella pneumoniae Sequence Types in Mexico Associated With Horizontal Transfer Mediated by IncF-Like Plasmids , 2021, Frontiers in Microbiology.

[9]  Dan Li,et al.  A set of shuttle plasmids for gene expression in Acinetobacter baumannii , 2021, PloS one.

[10]  P. Higgins,et al.  Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Major Endemic Clones in South America , 2020, Frontiers in Microbiology.

[11]  John H. E. Nash,et al.  Universal whole-sequence-based plasmid typing and its utility to prediction of host range and epidemiological surveillance , 2020, Microbial genomics.

[12]  R. Kaas,et al.  ResFinder 4.0 for predictions of phenotypes from genotypes , 2020, The Journal of antimicrobial chemotherapy.

[13]  R. Gutiérrez-Ríos,et al.  Structure and Evolution of Acinetobacter baumannii Plasmids , 2020, Frontiers in Microbiology.

[14]  S. Joshi,et al.  Distribution of carbapenem resistant Acinetobacter baumannii with blaADC-30 and induction of ADC-30 in response to beta-lactam antibiotics. , 2020, Research in microbiology.

[15]  S. Castillo-Ramírez,et al.  Origin of OXA-23 Variant OXA-239 from a Recently Emerged Lineage of Acinetobacter baumannii International Clone V , 2020, mSphere.

[16]  P. Nordmann,et al.  Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  S. Giono-Cerezo,et al.  Carbapenem-Resistant Acinetobacter baumannii in Three Tertiary Care Hospitals in Mexico: Virulence Profiles, Innate Immune Response and Clonal Dissemination , 2019, Front. Microbiol..

[18]  S. Giono-Cerezo,et al.  Emergence of IncFIA Plasmid-Carrying blaNDM-1 Among Klebsiella pneumoniae and Enterobacter cloacae Isolates in a Tertiary Referral Hospital in Mexico. , 2019, Microbial drug resistance.

[19]  A. Ferrera,et al.  Unexplored Genetic Diversity of Multidrug- and Extremely Drug-Resistant Acinetobacter baumannii Isolates from Tertiary Hospitals in Honduras. , 2019, Microbial drug resistance.

[20]  P. Bustos,et al.  Whole-Genome Sequences of Five Acinetobacter baumannii Strains From a Child With Leukemia M2 , 2019, Front. Microbiol..

[21]  S. Partridge,et al.  Mobile Genetic Elements Associated with Antimicrobial Resistance , 2018, Clinical Microbiology Reviews.

[22]  James Robertson,et al.  MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies , 2018, Microbial genomics.

[23]  M. J. Pons,et al.  Emergence and spread of carbapenem-resistant Acinetobacter baumannii international clones II and III in Lima, Peru , 2018, Emerging Microbes & Infections.

[24]  M. Nastro,et al.  Carbapenemases in Acinetobacter baumannii. Review of their dissemination in Latin America. , 2018, Revista Argentina de microbiologia.

[25]  M. Feldman,et al.  Uncovering the mechanisms of Acinetobacter baumannii virulence , 2017, Nature Reviews Microbiology.

[26]  Luis F. Lozano,et al.  Rapid Gene Turnover as a Significant Source of Genetic Variation in a Recently Seeded Population of a Healthcare-Associated Pathogen , 2017, Front. Microbiol..

[27]  M. Adams,et al.  Nosocomial Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Isolates Containing blaOXA-237 Carried on a Plasmid , 2017, Antimicrobial Agents and Chemotherapy.

[28]  C. Yeo,et al.  Small, Enigmatic Plasmids of the Nosocomial Pathogen, Acinetobacter baumannii: Good, Bad, Who Knows? , 2017, Front. Microbiol..

[29]  M. Hackel,et al.  Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013–2015 , 2017, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[30]  Jung Hun Lee,et al.  Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options , 2017, Front. Cell. Infect. Microbiol..

[31]  R. Bonomo,et al.  Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges , 2016, Clinical Microbiology Reviews.

[32]  Dmitry Antipov,et al.  plasmidSPAdes: Assembling Plasmids from Whole Genome Sequencing Data , 2016, bioRxiv.

[33]  H. Barrios,et al.  Outbreak Caused by blaOXA-72-Producing Acinetobacter baumannii ST417 Detected in Clinical and Environmental Isolates. , 2016, Microbial drug resistance.

[34]  E. A. Rodríguez,et al.  [Carbapenem-resistant Acinetobacter baumannii causing osteomyelitis and infections of skin and soft tissues in hospitals of Medellín, Colombia]. , 2015, Biomedica : revista del Instituto Nacional de Salud.

[35]  César Domínguez,et al.  GelJ – a tool for analyzing DNA fingerprint gel images , 2015, BMC Bioinformatics.

[36]  H. Barrios,et al.  Genetic characterisation of drug resistance and clonal dynamics of Acinetobacter baumannii in a hospital setting in Mexico. , 2015, International journal of antimicrobial agents.

[37]  P. Loewen,et al.  Genome Sequence of an Extremely Drug-Resistant Clinical Isolate of Acinetobacter baumannii Strain AB030 , 2014, Genome Announcements.

[38]  L. Garcia-Torres,et al.  Molecular mechanisms associated with nosocomial carbapenem-resistant Acinetobacter baumannii in Mexico. , 2014, Archives of medical research.

[39]  J. Silva-Sánchez,et al.  Identification of OXA-23 carbapenemases: novel variant OXA-239 in Acinetobacter baumannii ST758 clinical isolates in Mexico , 2014, New microbes and new infections.

[40]  Katherina C. Chua,et al.  Whole-Genome Sequence Analysis of the Naturally Competent Acinetobacter baumannii Clinical Isolate A118 , 2014, Genome biology and evolution.

[41]  T. P. G. Chagas,et al.  Characterization of carbapenem-resistant Acinetobacter baumannii in Brazil (2008-2011): countrywide spread of OXA-23-producing clones (CC15 and CC79). , 2014, Diagnostic microbiology and infectious disease.

[42]  Torsten Seemann,et al.  Prokka: rapid prokaryotic genome annotation , 2014, Bioinform..

[43]  J. Piesker,et al.  DNA Uptake by the Nosocomial Pathogen Acinetobacter baumannii Occurs during Movement along Wet Surfaces , 2013, Journal of bacteriology.

[44]  P. Nordmann,et al.  Strategies for identification of carbapenemase-producing Enterobacteriaceae. , 2013, The Journal of antimicrobial chemotherapy.

[45]  Sergey I. Nikolenko,et al.  SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing , 2012, J. Comput. Biol..

[46]  M. Falagas,et al.  Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[47]  L. Dijkshoorn,et al.  The Population Structure of Acinetobacter baumannii: Expanding Multiresistant Clones from an Ancestral Susceptible Genetic Pool , 2010, PloS one.

[48]  Julio Collado-Vides,et al.  The partitioned Rhizobium etli genome: genetic and metabolic redundancy in seven interacting replicons. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[49]  P. Nordmann,et al.  Outbreak of Carbapenem-Resistant Acinetobacter baumannii Producing the Carbapenemase OXA-23 in a Tertiary Care Hospital of Papeete, French Polynesia , 2005, Journal of Clinical Microbiology.

[50]  F. Rodríguez-Valera,et al.  Development of a Multilocus Sequence Typing Scheme for Characterization of Clinical Isolates of Acinetobacter baumannii , 2005, Journal of Clinical Microbiology.

[51]  D H Persing,et al.  Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing , 1995, Journal of clinical microbiology.

[52]  T. Eckhardt,et al.  A rapid method for the identification of plasmid desoxyribonucleic acid in bacteria. , 1978, Plasmid.

[53]  L. R. Dice Measures of the Amount of Ecologic Association Between Species , 1945 .