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Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico.

ABSTRACT: Virulence profiles and innate immune responses were studied in Acinetobacter baumannii from nosocomial infections collected over one year in a tertiary care hospital in Mexico. A. baumannii were identified by VITEK 2 System followed by susceptibility tests. Carbapenemase genes, active efflux mechanism to imipenem and meropenem and outer membrane proteins profile were analyzed to evaluate their role on the activity of carbapenem resistance. All isolates were genotyped by pulsed field gel electrophoresis. The ability to form biofilm was determined on a polystyrene surface. The resistance to complement was determined with a pooled human normal serum and TNF? release by infected macrophages was determined by ELISA. The 112 isolates from this study were associated with a 52% of mortality. All were resistance to ?-lactams, fluoroquinolones, and trimethroprim-sulfamethoxal, 96 and 90% were resistant to meropenem and imipenem, respectively, but with high susceptibility to polymyxin B, colistin and tigecyclin. Isolates were classified in 11 different clones. Most isolates, 88% (99/112), were metallo-?-lactamases and carbapenemases producers, associated in 95% with the presence of blaOXA-72 gene. Only 4/99 and 1/99 of the carbapenem-resistant isolates were related to efflux mechanism to meropenem or imipenem resistance, respectively. The loss of expression of 22, 29, and/or 33-36-kDa proteins was detected in 8/11 of the clinical isolates with resistance to carbapenem. More than 96% (108/112) of the isolates were high producers of biofilms on biotic surfaces. Finally, all isolates showed variable resistance to normal human serum activity and were high inductors of TNF? release by macrophages. In summary, these results suggest that multidrug-resistant A. baumannii can persist in the hospital environment through its ability to form biofilms. The high mortality observed was due to their ability to survive normal human serum activity and capability to induce potent inflammatory immune response making this nosocomial pathogen a serious threat to hospitalized patients.

SUBMITTER: Rosales-Reyes R

PROVIDER: S-EPMC5552319 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico.

Rosales-Reyes Roberto R Gayosso-Vázquez Catalina C Fernández-Vázquez José Luis JL Jarillo-Quijada Ma Dolores MD Rivera-Benítez César C Santos-Preciado José Ignacio JI Alcántar-Curiel María Dolores MD

PloS one 20170810 8

Virulence profiles and innate immune responses were studied in Acinetobacter baumannii from nosocomial infections collected over one year in a tertiary care hospital in Mexico. A. baumannii were identified by VITEK 2 System followed by susceptibility tests. Carbapenemase genes, active efflux mechanism to imipenem and meropenem and outer membrane proteins profile were analyzed to evaluate their role on the activity of carbapenem resistance. All isolates were genotyped by pulsed field gel electrop ...[more]

PMID: 28797068

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Project description:Acinetobacter baumannii is one of the most important nosocomial pathogens distributed worldwide. Due to its multidrug-resistance and the propensity for the epidemic spread, the World Health Organization includes this bacterium as a priority health issue for development of new antibiotics. The aims of this study were to investigate the antimicrobial resistance profile, the clonal relatedness, the virulence profiles, the innate host immune response and the clonal dissemination of A. baumannii in Hospital Civil de Guadalajara (HCG), Hospital Regional General Ignacio Zaragoza (HRGIZ) and Pediatric ward of the Hospital General de México Eduardo Liceaga (HGM-P). A total of 252 A. baumannii clinical isolates were collected from patients with nosocomial infections in these hospitals between 2015 and 2016. These isolates showed a multidrug-resistant profile and most of them only susceptible to colistin. Furthermore, 83.3 and 36.9% of the isolates carried the bla OXA- 24 and bla TEM- 1 genes for resistance to carbapenems and ?-lactam antibiotics, respectively. The clonal relatedness assessed by pulsed-field gel electrophoresis (PFGE) and by multi-locus sequence typing (MLST) demonstrated a genetic diversity. Remarkably, the ST136, ST208 and ST369 that belonged to the clonal complex CC92 and ST758 and ST1054 to the CC636 clonal complex were identified. The ST136 was a high-risk persistent clone involved in an outbreak at HCG and ST369 were related to the first carbapenem-resistant A. baumannii outbreak in HRGIZ. Up to 58% isolates were able to attach to A549 epithelial cells and 14.5% of them induced >50% of cytotoxicity. A549 cells infected with A. baumannii produced TNF?, IL-6 and IL-1? and the oxygen and nitrogen reactive species that contributes to the development of an inflammatory immune response. Up to 91.3% of clinical isolates were resistant to normal human serum activity. Finally, 98.5% of the clinical isolates were able to form biofilm over polystyrene tubes. In summary, these results demonstrate the increasingly dissemination of multidrug-resistant A. baumannii clones in three hospitals in Mexico carrying diverse bacterial virulence factors that could contribute to establishment of the innate immune response associated to the fatality risks in seriously ill patients.

Project description:Acinetobacter baumannii is a major opportunistic pathogen causing hospital-acquired infections, and it is imperative to comprehend its evolutionary and epidemiological dynamics in hospitals to prevent and control nosocomial transmission. Here, we present a comprehensive genomic epidemiological study involving the genomic sequencing and antibiotic resistance profiling of 634 A. baumannii strains isolated from seven intensive care units (ICUs) of a Chinese general hospital over 2 consecutive years. Our study reveals that ST2 is highly dominant (90.54%) in the ICUs, with 98.90% of the ST2 exhibiting multidrug resistant or extensively drug resistant. Phylogenetic analyses of newly sequenced genomes and public data suggest that nosocomial isolates originated outside the hospital but evolved inside. The major lineages appear to be stable, with 9 of the 28 identified nosocomial epidemic clones infecting over 60% of the affected patients. However, outbreaks of two highly evolved clones have been observed in different hospitals, suggesting significant inter-hospital transmission chains. By coupling patient medical records and genomic divergence of the ST2, we found that cross-ward patient transfer played a crucial role in pathogen's nosocomial transmission. Additionally, we identified 831 potential adaptive evolutionary loci and 44 associated genes by grouping and comparing the genomes of clones with different prevalence. Overall, our study provides a comprehensive and contemporary survey on the epidemiology and genomic evolution of A. baumannii in a large Chinese general hospital. These findings shed light on the nosocomial evolution and transmission of A. baumannii and offers valuable information for transmission prevention and antibiotic therapy.IMPORTANCEThis study delved into the genomic evolution and transmission of nosocomial Acinetobacter baumannii on a large scale, spanning both an extended time period and the largest sample size to date. Through molecular epidemiological investigations based on genomics, we can directly trace the origin of the pathogen, detecting and monitoring outbreaks of infectious diseases in a timely manner, and ensuring public health safety. In addition, this study also collects a large amount of genomic and antibiotic resistance detection data, which is helpful for phenotype prediction based on genomic sequencing. It enables patients to receive personalized antibiotic treatment quickly, helps doctors select antibiotics more accurately, and contributes to reducing the use of antibiotics and lowering the risk of antibiotic resistance development.

Project description:Acinetobacter baumannii is an important nosocomial pathogen, which is multidrug resistant (MDR). Acinetobacter baumannii has become a major threat to public health worldwide due to its ability to easily acquire resistant genes. In order to analyze its epidemiology characteristics and the genetic evolution, A. baumannii isolates obtained from a Chinese tertiary hospital in the past 12 years (2008-2019), 295 isolates of non-repetitive A. baumannii, were recovered from patients and wards environments. The resistance genes were analyzed using antimicrobial susceptibility testing. The genetic relatedness of 295 isolates was identified by multilocus sequence typing (MLST) and eBURST analysis. It was found that the antibiotic-resistant and carbapenemase-resistant genes of all the 295 MDR A. baumannii in the hospital have not changed significantly over the past 12 years; all of them were resistant to multiple antibiotics except the polymyxin E and tigecycline. The results of drug-resistant genes showed that the detection rates of carbapenemase-resistant genes blaOXA-23, blaTEM-1, and blaOXA-66 were 97.6, 75.3, and 71.9%, respectively, which were detected almost every year from 2008 to 2019. Additionally, 16s rRNA methylation enzyme gene armA, aminoglycoside-resistant gene ant(3")-I, and class I integrase gene could also have a high positive rate. By MLST, these isolates were assigned to 12 sequence types (STs), including ST369, ST208, ST195, ST191, ST368, ST530, ST469, ST451, ST229, ST381, ST543, and ST1176. eBURST analysis showed that 9 STs with ST208 as the founder genotype belonged to Group 1 except for ST229, ST530, and ST1176. Therefore, most MDR A. baumannii isolates had a relatively close genetic relationship. Notably, the predominant ST208 and ST369 at the early stage changed to ST451 in 2019, indicating that the complex and diverse genetic background of the prevalence of A. baumannii isolates in the hospital. Overall, further epidemiological surveillance and genetic evolution analysis of A. baumannii are required, which can provide new strategies for the prevention and control of A. baumannii infections.

Dataset Information

Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico.

Publications

Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico.

Similar Datasets

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