Evaluating the role of Burkholderia pseudomallei K96243 toxins BPSS0390, BPSS0395, and BPSS1584 in persistent infection

Ross, Brittany N.; Micheva‐Viteva, Sofiya N.; Hong‐Geller, Elizabeth; Torres, Alfredo G.

doi:10.1111/cmi.13096

Title: Evaluating the role of Burkholderia pseudomallei K96243 toxins BPSS0390, BPSS0395, and BPSS1584 in persistent infection

Journal Article · Sat Aug 10 00:00:00 EDT 2019 · Cellular Microbiology

DOI:https://doi.org/10.1111/cmi.13096· OSTI ID:1572326

Ross, Brittany N. ^[1];

^[2];

^[1]

Univ. of Texas Medical Branch, Galveston, TX (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Burkholderia pseudomallei is the causative agent of melioidosis, a disease with a mortality rate of up to 40% even with treatment. Despite the ability of certain antibiotics to control initial infection, relapse occurs in treated patients. The inability of antibiotics to clear this bacterial infection is in part due to persistence, an evasion mechanism against antibiotics and the effect of host defenses. Evaluation of antibiotic efficacy against B. pseudomallei revealed that up to 48% of in vitro grown populations can survive in a persister state. Toxin–antitoxin (TA) systems have been previously implicated in modulating bacterial persistence. Here, we generated three isogenic TA mutants and found that loss of each toxin gene did not alter antibiotic persistence or macrophage survival. In response to macrophage–induced persistence, all three toxin mutants demonstrated increased intracellular susceptibility to levofloxacin which in part was due to the inability of the mutants to induce persistence after nitric oxide or nutrient starvation. In an inhalational model of murine melioidosis, both ΔBPSS0395 and ΔBPSS1584 strains were attenuated, and treatment with levofloxacin led to significant reduction in lung colonisation and reduced splenic colonisation by ΔBPSS0395. Based on our findings, these toxins deserve additional evaluation as putative therapeutic targets.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: Defense Threat Reduction Agency (DTRA); USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1572326

Report Number(s):: LA-UR-19-21497

Journal Information:: Cellular Microbiology, Vol. 21, Issue 12; ISSN 1462-5814

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 11 works

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