Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode

Victor Jimenez , Erik W. Settles, Bart Currie, Paul Keim, Fernando P. Monroy

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    Abstract

    Background: Binge drinking, an increasingly common form of alcohol use disorder, is associated with substantial morbidity and mortality; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol intoxication is increasingly being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure increased B. pseudomallei near-neighbor virulence in vivo and increased paracellular diffusion and intracellular invasion, no experimental studies have examined the extent to which bacterial and alcohol dosage play a role in disease progression. In addition, the temporal effects of a single binge alcohol dose prior to infection has not been examined in vivo.

    Principal findings: In this study, we used B. thailandensis E264 a close genetic relative of B. pseudomallei, as useful BSL-2 model system. Eight-week-old female C57BL/6 mice were utilized in three distinct animal models to address the effects of 1) bacterial dosage, 2) alcohol dosage, and 3) the temporal effects, of a single binge alcohol episode. Alcohol was administered comparable to human binge drinking (≤ 4.4 g/kg) or PBS intraperitoneally before a non-lethal intranasal infection. Bacterial colonization of lung and spleen was increased in mice administered alcohol even after bacterial dose was decreased 10-fold. Lung and not spleen tissue were colonized even after alcohol dosage was decreased 20 times below the U.S legal limit. Temporally, a single binge alcohol episode affected lung bacterial colonization for more than 24 h after alcohol was no longer detected in the blood. Pulmonary and splenic cytokine expression (TNF-α, GM-CSF) remained suppressed, while IL-12/p40 increased in mice administered alcohol 6 or 24 h prior to infection. Increased lung and not intestinal bacterial invasion was observed in human and murine non-phagocytic epithelial cells exposed to 0.2% v/v alcohol in vitro.

    Conclusions: Our results indicate that the effects of a single binge alcohol episode are tissue specific. A single binge alcohol intoxication event increases bacterial colonization in mouse lung tissue even after very low BACs and decreases the dose required to colonize the lungs with less virulent B. thailandensis. Additionally, the temporal effects of binge alcohol alters lung and spleen cytokine expression for at least 24 h after alcohol is detected in the blood. Delayed recovery in lung and not spleen tissue may provide a means for B. pseudomallei and near-neighbors to successfully colonize lung tissue through increased intracellular invasion of non-phagocytic cells in patients with hazardous alcohol intake.
    Original languageEnglish
    Article numbere0218147
    Pages (from-to)1-21
    Number of pages21
    JournalPLoS One
    Volume14
    Issue number12
    DOIs
    Publication statusPublished - 10 Dec 2019

    Fingerprint

    Burkholderia thailandensis
    Burkholderia
    alcohols
    lungs
    Alcohols
    Tissue
    Lung
    Burkholderia pseudomallei
    bacterial colonization
    dosage
    Spleen
    spleen
    Binge Drinking
    mice
    Alcoholic Intoxication
    tissues
    binging
    poisoning
    Infection
    cytokines

    Cite this

    Jimenez , Victor ; Settles, Erik W. ; Currie, Bart ; Keim, Paul ; P. Monroy, Fernando . / Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode. In: PLoS One. 2019 ; Vol. 14, No. 12. pp. 1-21.
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    title = "Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode",
    abstract = "Background: Binge drinking, an increasingly common form of alcohol use disorder, is associated with substantial morbidity and mortality; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol intoxication is increasingly being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure increased B. pseudomallei near-neighbor virulence in vivo and increased paracellular diffusion and intracellular invasion, no experimental studies have examined the extent to which bacterial and alcohol dosage play a role in disease progression. In addition, the temporal effects of a single binge alcohol dose prior to infection has not been examined in vivo.Principal findings: In this study, we used B. thailandensis E264 a close genetic relative of B. pseudomallei, as useful BSL-2 model system. Eight-week-old female C57BL/6 mice were utilized in three distinct animal models to address the effects of 1) bacterial dosage, 2) alcohol dosage, and 3) the temporal effects, of a single binge alcohol episode. Alcohol was administered comparable to human binge drinking (≤ 4.4 g/kg) or PBS intraperitoneally before a non-lethal intranasal infection. Bacterial colonization of lung and spleen was increased in mice administered alcohol even after bacterial dose was decreased 10-fold. Lung and not spleen tissue were colonized even after alcohol dosage was decreased 20 times below the U.S legal limit. Temporally, a single binge alcohol episode affected lung bacterial colonization for more than 24 h after alcohol was no longer detected in the blood. Pulmonary and splenic cytokine expression (TNF-α, GM-CSF) remained suppressed, while IL-12/p40 increased in mice administered alcohol 6 or 24 h prior to infection. Increased lung and not intestinal bacterial invasion was observed in human and murine non-phagocytic epithelial cells exposed to 0.2{\%} v/v alcohol in vitro.Conclusions: Our results indicate that the effects of a single binge alcohol episode are tissue specific. A single binge alcohol intoxication event increases bacterial colonization in mouse lung tissue even after very low BACs and decreases the dose required to colonize the lungs with less virulent B. thailandensis. Additionally, the temporal effects of binge alcohol alters lung and spleen cytokine expression for at least 24 h after alcohol is detected in the blood. Delayed recovery in lung and not spleen tissue may provide a means for B. pseudomallei and near-neighbors to successfully colonize lung tissue through increased intracellular invasion of non-phagocytic cells in patients with hazardous alcohol intake.",
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    Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode. / Jimenez , Victor; Settles, Erik W.; Currie, Bart; Keim, Paul; P. Monroy, Fernando .

    In: PLoS One, Vol. 14, No. 12, e0218147, 10.12.2019, p. 1-21.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode

    AU - Jimenez , Victor

    AU - Settles, Erik W.

    AU - Currie, Bart

    AU - Keim, Paul

    AU - P. Monroy, Fernando

    PY - 2019/12/10

    Y1 - 2019/12/10

    N2 - Background: Binge drinking, an increasingly common form of alcohol use disorder, is associated with substantial morbidity and mortality; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol intoxication is increasingly being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure increased B. pseudomallei near-neighbor virulence in vivo and increased paracellular diffusion and intracellular invasion, no experimental studies have examined the extent to which bacterial and alcohol dosage play a role in disease progression. In addition, the temporal effects of a single binge alcohol dose prior to infection has not been examined in vivo.Principal findings: In this study, we used B. thailandensis E264 a close genetic relative of B. pseudomallei, as useful BSL-2 model system. Eight-week-old female C57BL/6 mice were utilized in three distinct animal models to address the effects of 1) bacterial dosage, 2) alcohol dosage, and 3) the temporal effects, of a single binge alcohol episode. Alcohol was administered comparable to human binge drinking (≤ 4.4 g/kg) or PBS intraperitoneally before a non-lethal intranasal infection. Bacterial colonization of lung and spleen was increased in mice administered alcohol even after bacterial dose was decreased 10-fold. Lung and not spleen tissue were colonized even after alcohol dosage was decreased 20 times below the U.S legal limit. Temporally, a single binge alcohol episode affected lung bacterial colonization for more than 24 h after alcohol was no longer detected in the blood. Pulmonary and splenic cytokine expression (TNF-α, GM-CSF) remained suppressed, while IL-12/p40 increased in mice administered alcohol 6 or 24 h prior to infection. Increased lung and not intestinal bacterial invasion was observed in human and murine non-phagocytic epithelial cells exposed to 0.2% v/v alcohol in vitro.Conclusions: Our results indicate that the effects of a single binge alcohol episode are tissue specific. A single binge alcohol intoxication event increases bacterial colonization in mouse lung tissue even after very low BACs and decreases the dose required to colonize the lungs with less virulent B. thailandensis. Additionally, the temporal effects of binge alcohol alters lung and spleen cytokine expression for at least 24 h after alcohol is detected in the blood. Delayed recovery in lung and not spleen tissue may provide a means for B. pseudomallei and near-neighbors to successfully colonize lung tissue through increased intracellular invasion of non-phagocytic cells in patients with hazardous alcohol intake.

    AB - Background: Binge drinking, an increasingly common form of alcohol use disorder, is associated with substantial morbidity and mortality; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol intoxication is increasingly being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure increased B. pseudomallei near-neighbor virulence in vivo and increased paracellular diffusion and intracellular invasion, no experimental studies have examined the extent to which bacterial and alcohol dosage play a role in disease progression. In addition, the temporal effects of a single binge alcohol dose prior to infection has not been examined in vivo.Principal findings: In this study, we used B. thailandensis E264 a close genetic relative of B. pseudomallei, as useful BSL-2 model system. Eight-week-old female C57BL/6 mice were utilized in three distinct animal models to address the effects of 1) bacterial dosage, 2) alcohol dosage, and 3) the temporal effects, of a single binge alcohol episode. Alcohol was administered comparable to human binge drinking (≤ 4.4 g/kg) or PBS intraperitoneally before a non-lethal intranasal infection. Bacterial colonization of lung and spleen was increased in mice administered alcohol even after bacterial dose was decreased 10-fold. Lung and not spleen tissue were colonized even after alcohol dosage was decreased 20 times below the U.S legal limit. Temporally, a single binge alcohol episode affected lung bacterial colonization for more than 24 h after alcohol was no longer detected in the blood. Pulmonary and splenic cytokine expression (TNF-α, GM-CSF) remained suppressed, while IL-12/p40 increased in mice administered alcohol 6 or 24 h prior to infection. Increased lung and not intestinal bacterial invasion was observed in human and murine non-phagocytic epithelial cells exposed to 0.2% v/v alcohol in vitro.Conclusions: Our results indicate that the effects of a single binge alcohol episode are tissue specific. A single binge alcohol intoxication event increases bacterial colonization in mouse lung tissue even after very low BACs and decreases the dose required to colonize the lungs with less virulent B. thailandensis. Additionally, the temporal effects of binge alcohol alters lung and spleen cytokine expression for at least 24 h after alcohol is detected in the blood. Delayed recovery in lung and not spleen tissue may provide a means for B. pseudomallei and near-neighbors to successfully colonize lung tissue through increased intracellular invasion of non-phagocytic cells in patients with hazardous alcohol intake.

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