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Pathogens 2016, 5(1), 20; doi:10.3390/pathogens5010020

Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli

1
Department of Pathology, University of Utah, 15 N. Medical Drive E., Salt Lake City, UT 84112, USA
2
Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
*
Author to whom correspondence should be addressed.
Received: 12 November 2015 / Accepted: 5 February 2016 / Published: 14 February 2016
(This article belongs to the Special Issue Molecular Aspects of Urinary Tract Infection)
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Abstract

Histone deacetylase 6 (HDAC6) is a non-canonical, mostly cytosolic histone deacetylase that has a variety of interacting partners and substrates. Previous work using cell-culture based assays coupled with pharmacological inhibitors and gene-silencing approaches indicated that HDAC6 promotes the actin- and microtubule-dependent invasion of host cells by uropathogenic Escherichia coli (UPEC). These facultative intracellular pathogens are the major cause of urinary tract infections. Here, we examined the involvement of HDAC6 in bladder colonization by UPEC using HDAC6 knockout mice. Though UPEC was unable to invade HDAC6−/− cells in culture, the bacteria had an enhanced ability to colonize the bladders of mice that lacked HDAC6. This effect was transient, and by six hours post-inoculation bacterial titers in the HDAC6−/− mice were reduced to levels seen in wild type control animals. Subsequent analyses revealed that the mutant mice had greater bladder volume capacity and fluid retention, along with much higher levels of acetylated a-tubulin. In addition, infiltrating neutrophils recovered from the HDAC6−/− bladder harbored significantly more viable bacteria than their wild type counterparts. Cumulatively, these changes may negate any inhibitory effects that the lack of HDAC6 has on UPEC entry into individual host cells, and suggest roles for HDAC6 in other urological disorders such as urinary retention. View Full-Text
Keywords: histone deacetylase 6; bladder; neutrophil; invasion; UTI; urothelium; microtubules histone deacetylase 6; bladder; neutrophil; invasion; UTI; urothelium; microtubules
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lewis, A.J.; Dhakal, B.K.; Liu, T.; Mulvey, M.A. Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli. Pathogens 2016, 5, 20.

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