Macrophage environment turns otherwise MccJ25-resistant Salmonella into sensitive

BMC Microbiology

Research Article

Ricardo N Farías¹  Paula A Vincent¹  Mónica A Delgado¹  Conrado Adler¹  María Fernanda Pomares¹  Ricardo de Cristóbal¹  Natalia S Corbalán¹ 

[1] Instituto Superior de Investigaciones Biológicas (Concejo Nacional de Investigación Científica y Técnica-Universidad Nacional de Tucumán) and Instituto de Química Biológica “Dr. Bernabe Bloj”, Chacabuco 461, San Miguel de Tucumán, 4000, Tucumán, Argentina;

关键词: Microcin J25;    Salmonella;    FhuA;    Low pH;   

DOI  :  10.1186/1471-2180-13-95

 received in 2013-01-23, accepted in 2013-04-22,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMicrocin J25 (MccJ25) is a plasmid-encoded antibiotic peptide produced by Escherichia coli (E. coli). MccJ25 enters into the sensitive E. coli strains by the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbB, ExbD and SbmA. The resistance of Salmonella enterica serovar Typhimurium (S. Typhimurium) to MccJ25 is attributed to the inability of its FhuA protein to incorporate the antibiotic into the cell.ResultsIn this work we demonstrate that S. Typhimurium becomes notably susceptible to MccJ25 when replicating within macrophages. In order to determine the possible cause of this phenomenon, we studied the sensitivity of S. Typhimurium to MccJ25 at conditions resembling those of the internal macrophage environment, such as low pH, low magnesium and iron deprivation. We observed that the strain was only sensitive to the antibiotic at low pH, leading us to attribute the bacterial sensitization to this condition. A MccJ25-resistant E. coli strain in which fhuA is deleted was also inhibited by the antibiotic at low pH. Then, we could assume that the MccJ25 sensitivity change observed in both E. coli fhuA and S. Typhimurium is mediated by a MccJ25 uptake independent of the FhuA receptor. Moreover, low pH incubation also sensitized S. Typhimurium to the hydrophobic antibiotic novobiocin, which does not affect enteric bacteria viability because it is unable to penetrate the bacterial outer membrane. This observation supports our hypothesis about low pH producing a modification in the bacterial membrane permeability that allows an unspecific MccJ25 uptake. On the other hand, MccJ25 inhibited S. Typhimurium when cells were preincubated in acidic pH medium and then treated at neutral pH with the antibiotic.ConclusionsOur results suggest that acidic condition does not alter MccJ25 hydrophobicity but irreversibly modifies bacterial membrane permeability. This would allow an unspecific antibiotic uptake into the cell.From our data it is possible to infer that intracellular pathogenic strains, which are in vitro resistant to MccJ25, could become susceptible ones in vivo. Therefore, the MccJ25 action spectrum would be broader than what in vitro experiments indicate.

【 授权许可】

Unknown   
© Pomares et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.