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

• Published in: PloS one Vol. 12; no. 8; p. e0182899
• Main Authors: Rosales-Reyes, Roberto, Gayosso-Vázquez, Catalina, Fernández-Vázquez, José Luis, Jarillo-Quijada, Ma Dolores, Rivera-Benítez, César, Santos-Preciado, José Ignacio, Alcántar-Curiel, María Dolores
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.08.2017; Public Library of Science (PLoS)
• Subjects: Acinetobacter; Acinetobacter baumannii - drug effects; Acinetobacter baumannii - isolation & purification; Acinetobacter baumannii - pathogenicity; Acinetobacter Infections - drug therapy; Acinetobacter Infections - metabolism; Analysis; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; beta-Lactamases - metabolism; Biofilms; Biology and Life Sciences; Carbapenemase; Carbapenems - metabolism; Cell division; Clinical isolates; Colistin; Cross Infection - drug therapy; Cross Infection - metabolism; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Efflux; Enzyme-linked immunosorbent assay; Fluoroquinolones; Gel electrophoresis; Genes; Genetic aspects; Health aspects; Hospitals; Humans; Imipenem; Immune response; Immune system; Immunity, Innate; Inductors; Infectious diseases; Inflammation; Innate immunity; Macrophages; Medicine and Health Sciences; Membrane proteins; Meropenem; Metallography; Mexico; Microbial drug resistance; Microbial Sensitivity Tests; Mortality; Multidrug resistance; Multidrug resistant organisms; Nosocomial infection; Nosocomial infections; Outer membrane proteins; Pathogens; People and places; Polymyxin B; Polystyrene; Polystyrene resins; Proteins; Research and Analysis Methods; Risk factors; Surface chemistry; Tertiary Care Centers; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Virulence; Mexico
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182899

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 TNFα 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 β-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-β-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 TNFα 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.