Molecular and epidemiological investigation of a colistin-resistant OXA-23-/NDM-1-producing Acinetobacter baumannii outbreak in the Southwest Indian Ocean Area.

Dual resistance to colistin and carbapenems is a milestone reached by certain extensively-drug resistant (XDR) Gram-negative bacteria. This study describes the first outbreak of XDR colistin- and carbapenem-resistant OXA-23-/NDM-1-producing Acinetobacter baumannii (CCRAB) in the European overseas territory of Reunion Island (France, Indian Ocean). Between April 2019 and June 2020, 13 patients admitted to the University Hospital of Reunion Island were involved in the outbreak, of whom eight were infected and six died. The first case was traced to a medical evacuation from Mayotte Island (Comoros archipelago). An epidemiological link could be established for 11 patients. All of the collected CCRAB isolates showed the same resistance profile and co-produced intrinsic ß-lactamases OXA-69 and ADC-191, together with acquired carbapenem-hydrolysing ß-lactamases OXA-23 and NDM-1. A mutation likely involved in colistin resistance was detected in the two-component system PmrAB (D82N in PmrA). All of the isolates were found to belong to STPas1/STOx231 clonal complex and were phylogenetically indistinguishable. Their further characterization by whole-genome sequence analyses (whole-genome multi-locus sequence typing, single nucleotide polymorphisms) provided hints about the transmission pathways. This study pleads for strict application of control and prevention measures in institutions where the risk of imported XDR bacteria is high.

Acinetobacter baumannii up-regulates LncRNA-GAS5 and promotes the degradation of STX17 by blocking the activation of YY1.

Acinetobacter baumanniitriggers autophagy, affects the degradation of autophagy, and causes severe inflammatory injury. LncRNA growth arrest-specific transcript 5 (LncRNA-GAS5) and Yin and Yang 1 (YY1) are known to play an important role in the regulation of autophagy, however, the precise role of LncRNA-GAS5 and YY1 in the damage to autophagy caused by Acinetobacter baumanniiremains unclear. The aim of this study was to investigate the role of LncRNA-GAS5 and YY1 in the regulation of autophagy induced by Acinetobacter baumannii. We found that LncRNA-GAS5 was up-regulated following infection with Acinetobacter baumannii, thus resulting in the degradation of STX17, autophagy disorders, and the aggravated replication of Acinetobacter baumannii. We also analyzed the mechanism of interaction between LncRNA-GAS5 and YY1 and found that YY1 regulated its expression in a negative manner by binding to the promoter of LncRNA-GAS5. LncRNA-GAS5 and YY1 had opposite effects on the expression of STX17, this process maintained the stable expression of STX17. Following Acinetobacter baumannii infection, YY1 was down regulated and then separated from the binding region of LncRNA-GAS5, thus resulting in the activation of LncRNA-GAS5 transcription and reduction in STX17 protein expression. Finally, we infected LncRNA-GAS5 knockdown mice with Acinetobacter baumannii, the expression levels of IFN-ß in the lungs increased significantly, this alleviated lung injury. In conclusion, our work demonstrated the mechanism by which Acinetobacter baumannii infection can cause the degradation of STX17. We also demonstrated that LncRNA-GAS5 may be a potential therapeutic target for the treatment of lung injury induced by Acinetobacter baumannii.

Treatment strategy by lactoperoxidase and lactoferrin combination: Immunomodulatory and antibacterial activity against multidrug-resistant Acinetobacter baumannii.

Lactoperoxidase (Lpo) and Lactoferrin (Lf) were extracted from camel colostrum milk and purified. The antibacterial activity of the two purified proteins was estimated against 14 isolates of multidrug resistance Acinetobacter baumannii. A combination of Lpo and Lf exhibited bactericidal action against A. baumannii in vitro. A mouse model of acute A. baumannii pneumonia was improved. The injection of combined Lpo and Lf after infection leads to significant clearance of A. baumannii rates in lung as well as blood culture P < 0.05 in comparing with control. Furthermore, the results showed a significant P < 0.05 reduction in the Bronchoalveolar lavage albumin concentration, lung injury and lactate dehydrogenase activity in comparing with control. In addition, the combination of Lpo and Lf treatment induced substantial elevation of IL-4 and IL10 concentrations p < 0.0 5 that helped to prevent damage caused by the inflammatory response. We concluded that combination of Lpo and Lf had a major inhibition effect against A. baumannii in comparing with imipenem as well as their immunomodulatory activity against resistant A. baumannii was increased by a synergistic effect of them as a crude combination. This study indicated two combined proteins consider as crucial strategy for practical treatment of pneumonia in the future.

Clinical and molecular microbiological characteristics of carbapenem-resistant Acinetobacter baumannii strains in an NICU.

BACKGROUND: Seventeen cases of Acinetobacter baumannii infection in a neonatal intensive care unit (NICU) were evaluated. The strains were characterized as resistant to carbapenems. The aim of the present study was therefore to investigate the clinical and molecular epidemiological characteristics of the 17 carbapenem-resistant A. baumannii strains. METHODS: Samples were isolated from blood or sputum from the patients in the NICU, cultured using conventional techniques and an automated system. Multiplex polymerase chain reaction (PCR) was used to detect blaOXA-51-like, blaOXA-23-like, OXA-24, OXA-58 and Ambler class B carbapenemases. The genotype of the strains was identified on pulsed-field gel electrophoresis (PFGE). RESULTS: BlaOXA-23 was detected in all of the isolates. PFGE genotype analysis suggested three clones among the 17 strains. Two clones were isolated from other wards of the hospital including the adult ICU and Department of Pulmonology. The other clone was proved to be the first appearance in the hospital as genotype analysis. CONCLUSION: BlaOXA-23 was the drug-resistant gene that made A. baumannii resistant to carbepenem. The source of blaOXA-23 in the 17 isolates was different.