Abstract

Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Currently, no experimental studies have investigated the effects of binge alcohol on the adaptive immune system during an active infection. In this study, we used B. thailandensis and B. vietnamiensis, to investigate the impact of a single binge alcohol episode on the humoral response during infection. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking (4.4 g/kg) or PBS intraperitoneally 30 min before intranasal infection. Mice infected with B. thailandensis had a 100% survival rate, while those infected with B. vietnamiensis had a 33% survivability rate when a binge alcohol dose was administered. B. thailandensis was detected in blood of mice administered alcohol at only 7 days post infection (PI), while those infected with B. vietnamiensis and receiving alcohol were found throughout the 28-day infection as well as in tissues at day 28 PI. Binge alcohol elevated IgM and delayed IgG specific to the whole cell lysate (WCL) of B. vietnamiensis but not B. thailandensis infections. Differences in immunogenicity of B. pseudomallei near-neighbors provide a framework for novel insights into the effects of binge alcohol’s suppression of the humoral immune response that can cause opportunistic infections in otherwise healthy hosts.

Highlights

  • Burkholderia pseudomallei (B. pseudomallei), a gram-negative soil-borne bacterium, is the causative agent of melioidosis [1], a disease endemic in Northern Australia and Southeast Asia with an increasing presence in tropical regions globally [2]

  • Unlike chronic alcoholism or more severe alcohol use disorders (AUDs), studies in both human and animal models indicate that binge alcohol intoxication is a risky pattern characterized by the consumption of 4–6 standard drinks or reaching a minimum blood alcohol concentration (BAC) of 0.08% or higher within a 2–3-h drinking episode [7]

  • Our research sought to investigate the effects of binge alcohol intoxication, utilizing a murine model and two different Burkholderia species: B. thailandensis E264, a genetically similar strain to B. pseudomallei [16] and B. vietnamiensis, a known human pathogen found in the B. cepacia complex that commonly infects cystic fibrosis patients [17]

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Summary

Introduction

Burkholderia pseudomallei (B. pseudomallei), a gram-negative soil-borne bacterium, is the causative agent of melioidosis [1], a disease endemic in Northern Australia and Southeast Asia with an increasing presence in tropical regions globally [2]. Our research sought to investigate the effects of binge alcohol intoxication, utilizing a murine model and two different Burkholderia species: B. thailandensis E264, a genetically similar strain to B. pseudomallei [16] and B. vietnamiensis, a known human pathogen found in the B. cepacia complex that commonly infects cystic fibrosis patients [17]. By using both of these bacteria, we were able to show different perspectives as to how binge alcohol intoxication impacts the B-cell mediated humoral immune responses and allows less-pathogenic Burkholderia spp. the ability to persist and cause infection in vivo. Our results indicated that there was a delay and significant suppression in IgG in the infected and alcohol treated mice compared to that of infected but non-alcohol treated

Animals for Study
Bacterial Preparation
Enzyme-Linked Immunosorbent Assay
MagPix Detection Assays
Bead-Based Assay for IgM and IgG Antibodies
Data Analysis
Results
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