Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient

Abstract

Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P. aeruginosa from the gut. Meropenem treatment for a suspected urinary tract infection selected for elevated resistance in both the gut and lung. However, resistance was driven by parallel evolution in the gut and lung coupled with organ specific selective pressures, and translocation had only a minor impact on AMR. These findings suggest that reducing intestinal colonization of Pseudomonas may be an effective way to prevent lung infections in critically ill patients.

A specific innate immune response silences the virulence ofPseudomonas aeruginosain a latent infection model in theDrosophila melanogasterhost

“…Its prevalence is however increased in hospital settings, especially intensive care units and also in infants born in hospitals (Chuang et al, 2017; Markou and Apidianakis, 2014; Yoshioka et al, 1983). Actually, lung infections can originate from P. aeruginosa bacteria translocating from the gut (Wheatley et al, 2022; Zaborina et al, 2006). This pathogen is also often found in the digestive tract of cancer patients (Markou and Apidianakis, 2014) and may cause systemic infections in neutropenic patients with hematologic malignancies (Okuda et al, 2010).…”

The Lung Microbiome in Carcinogenesis and Immunotherapy Treatment

“…19 Indeed, subclinical microaspiration as well as transmigration from the gut to the lung has been shown to occur regularly in healthy subjects. [21][22][23] The process of elimination is a combination of mucociliary clearance, the cough reflex, and clearance by local immune effector cells. Dickson et al 20 have proposed the adapted island model of lung biogeography, in which the entire respiratory tract represents a continuous ecosystem that is derived from a single-source community.…”

“…Microbial immigration is mediated by microaspiration and direct inhalation from the air, although microaspiration is thought to be a prevailing mechanism given similarities between the composition of the oral and lung microbiome 19 . Indeed, subclinical microaspiration as well as transmigration from the gut to the lung has been shown to occur regularly in healthy subjects 21–23 . The process of elimination is a combination of mucociliary clearance, the cough reflex, and clearance by local immune effector cells.…”

Ten common misconceptions about antibiotic use in the hospital

“…Reducing multidrug-resistant organism intestinal colonization by reducing the usage of antibacterials represents an effective way in preventing pulmonary infections from multidrug-resistant organisms in ill patients. 44 Outside of perioperative prophylaxis, antibacterials are rarely effective in preventing infection in hospitalized patients. For example, prophylactic antibacterial therapy is prescribed to approximately 75% of hospitalized patients with acute aspiration events, although no reduction in mortality or reduced length of stays in critical care units has been observed.…”

“…Translocation of resistant bacteria occurs between different sites of the body. Reducing multidrug‐resistant organism intestinal colonization by reducing the usage of antibacterials represents an effective way in preventing pulmonary infections from multidrug‐resistant organisms in ill patients 44 …”