AUTHOR=Loughman Kathleen , Hall Jesse , Knowlton Samantha , Sindeldecker Devin , Gilson Tricia , Schmitt Deanna M. , Birch James W.-M. , Gajtka Tara , Kobe Brianna N. , Florjanczyk Aleksandr , Ingram Jenna , Bakshi Chandra S. , Horzempa Joseph 

TITLE=Temperature-Dependent Gentamicin Resistance of Francisella tularensis is Mediated by Uptake Modulation

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00037

DOI=10.3389/fmicb.2016.00037

ISSN=1664-302X

ABSTRACT=<p>Gentamicin (Gm) is an aminoglycoside commonly used to treat bacterial infections such as tularemia – the disease caused by <italic>Francisella tularensis</italic>. In addition to being pathogenic, <italic>F. tularensis</italic> is found in environmental niches such as soil where this bacterium likely encounters Gm producers (<italic>Micromonospora</italic> sp.). Here we show that <italic>F. tularensis</italic> exhibits increased resistance to Gm at ambient temperature (26°C) compared to mammalian body temperature (37°C). To evaluate whether <italic>F. tularensis</italic> was less permeable to Gm at 26°C, a fluorescent marker [Texas Red (Tr)] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26°C showed reduced fluorescence compared to those at 37°C when exposed to Tr-Gm suggesting that uptake of Gm was reduced at 26°C. Unconjugated Gm competitively inhibited uptake of Tr-Gm, demonstrating that this fluorescent compound was taken up similarly to unconjugated Gm. Lysates of <italic>F. tularensis</italic> bacteria incubated with Gm at 37°C inhibited the growth of <italic>Escherichia coli</italic> significantly more than lysates from bacteria incubated at 26°C, further indicating reduced uptake at this lower temperature. Other facultative pathogens (<italic>Listeria monocytogenes</italic> and <italic>Klebsiella pneumoniae</italic>) exhibited increased resistance to Gm at 26°C suggesting that the results generated using <italic>F. tularensis</italic> may be generalizable to diverse bacteria. Regulation of the uptake of antibiotics provides a mechanism by which facultative pathogens survive alongside antibiotic-producing microbes in nature.</p>