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Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth against Meropenem in a Murine Thigh Infection Model
Department of Microbiology, Medical School, University of Thessaly, Larissa 41110, Greece
Department of Microbiology, Medical School, University of Athens, Athens 11527, Greece
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 14 January 2013; in revised form: 16 February 2013 / Accepted: 1 March 2013 / Published: 11 March 2013
Abstract: Acinetobacter baumannii may exhibit phenotypic heterogeneous growth under exposure to antibiotics. We investigated the in vitro characteristics of A. baumannii isolates grown heterogeneously in the presence of meropenem and their virulence evaluated in experimental infections treated with meropenem. Five clinical A. baumannii isolates and the respective heterogeneously grown subpopulations were tested by agar dilution minimum inhibitory concentration (MIC) testing, pulsed field gel electrophoresis (PFGE), population analysis using meropenem and growth curves. The virulence of isolates and the therapeutic efficacy of three meropenem dosing schemes was evaluated in a neutropenic murine thigh infection model. The clinical isolates were meropenem-susceptible (MICs 1 to 4 mg/liter) and exhibited three distinct PFGE patterns. In all clinical isolates, population analysis yielded heterogeneously grown colonies. After seven subcultures in antibiotic-free media, resistant MIC levels were retained in two isolates (heteroresistant), while three isolates were reversed to susceptible MICs (persisters). Clinical isolates and heterogeneous subpopulations had similar growth rates. The heterogeneously grown A. baumannii subpopulations had reduced virulence, killing considerably fewer animals than the respective clinical isolates without treatment. The meropenem treatment outcome was similar in infections caused by the clinical and the heterogeneous isolates, irrespective to their MICs. In vitro meropenem exposure induces phenotypic heterogeneous growth in A. baumannii. Compared with the parental clinical isolates, the heterogeneously grown subpopulations exhibited lower virulence, killing fewer mice and responding equally to meropenem treatment, despite their higher MICs.
Keywords: heteroresistance; persisters; virulence; experimental infections
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MDPI and ACS Style
Neou, E.; Michail, G.; Tsakris, A.; Pournaras, S. Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth against Meropenem in a Murine Thigh Infection Model. Antibiotics 2013, 2, 73-82.
Neou E, Michail G, Tsakris A, Pournaras S. Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth against Meropenem in a Murine Thigh Infection Model. Antibiotics. 2013; 2(1):73-82.
Neou, Evangelia; Michail, George; Tsakris, Athanassios; Pournaras, Spyros. 2013. "Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth against Meropenem in a Murine Thigh Infection Model." Antibiotics 2, no. 1: 73-82.