Abstract
Acinetobacter baumannii has been recognized as a critical pathogen that causes severe infections worldwide not only because of the emergence of extensively drug-resistant (XDR) derivatives, but also because of its ability to persist in medical environments and colonize compromised patients. While there are numerous reports describing the mechanisms by which this pathogen acquires resistance genes, little is known regarding A. baumannii’s virulence functions associated with rare manifestations of infection such as necrotizing fasciitis, making the determination and implementation of alternative therapeutic targets problematic. To address this knowledge gap, this report describes the analysis of the NFAb-1 and NFAb-2 XDR isolates, which were obtained at two time points during a fatal case of necrotizing fasciitis, at the genomic and functional levels. The comparative genomic analysis of these isolates with the ATCC 19606T and ATCC 17978 strains showed that the NFAb-1 and NFAb-2 isolates are genetically different from each other as well as different from the ATCC 19606T and ATCC 17978 clinical isolates. These genomic differences could be reflected in phenotypic differences observed in these NFAb isolates. Biofilm, cell viability and flow cytometry assays indicate that all tested strains caused significant decreases in A549 human alveolar epithelial cell viability with ATCC 17978, NFAb-1 and NFAb-2 producing significantly less biofilm and significantly more hemolysis and capacity for intracellular invasion than ATCC 19606T. NFAb-1 and NFAb-2 also demonstrated negligible surface motility but significant twitching motility compared to ATCC 19606T and ATCC 17978, likely due to the presence of pili exceeding 2 µm in length, which are significantly longer and different from those previously described in the ATCC 19606T and ATCC 17978 strains. Interestingly, infection with cells of the NFAb-1 isolate, which were obtained from a premortem blood sample, lead to significantly higher mortality rates than NFAb-2 bacteria, which were obtained from postmortem tissue samples, when tested using the Galleria mellonella in vivo infection model. These observations suggest potential changes in the virulence phenotype of the A. baumannii necrotizing fasciitis isolates over the course of infection by mechanisms and cell processes that remain to be identified.
Highlights
The Gram-negative opportunistic human pathogen Acinetobacter baumannii is recognized by the Centers for Disease Control and Prevention and the World Health Organization as an urgent threat to public health and a critical priority for which the development of new antibiotics is crucially needed, respectively (Tacconelli et al, 2018; Moubareck and Halat, 2020)
The first isolate obtained from blood was designated NFAb-1 (Necrotizing Fasciitis Acinetobacter baumannii isolate 1), and the second isolate collected from postmortem tissue was designated NFAb-2 (Necrotizing Fasciitis Acinetobacter baumannii isolate 2)
The NFAb-1 isolate displayed the highest virulence when compared with all other strains with a killing rate higher than 90% five days after infection which was significantly greater than ATCC 19606T (P < 0.0001). These results indicate that the virulence properties between the necrotizing fasciitis isolates are as variable as those displayed by the ATCC strains, which are considered old isolates that are more susceptible to antibiotics and less virulent when compared with more contemporaneous clinical isolates
Summary
The Gram-negative opportunistic human pathogen Acinetobacter baumannii is recognized by the Centers for Disease Control and Prevention and the World Health Organization as an urgent threat to public health and a critical priority for which the development of new antibiotics is crucially needed, respectively (Tacconelli et al, 2018; Moubareck and Halat, 2020). Infections with A. baumannii isolates resistant to carbapenems, antibiotics commonly used for the treatment of infections caused by this pathogen, resulted in 8,500 hospitalizations and 700 deaths in the United States alone during 2017 with approximately 281 million dollars in associated healthcare costs. This bacterial pathogen is most commonly associated with severe nosocomial infections including pneumonia, urinary tract infections, and sepsis (Wong et al, 2017). At least ten more cases of human necrotizing fasciitis with A. baumannii as the sole etiological agent have been described in the literature (Corradino et al, 2010; Salvador et al, 2010; Sullivan et al, 2010; Wagner et al, 2011; Clemente et al, 2012; DeMuro et al, 2012; Hachimi et al, 2013; Oymacı et al, 2014; Sinha et al, 2014; Nehme et al, 2018; Rebai et al, 2018; Goret et al, 2019; Matthews et al, 2019)
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