Bacteria are not only acquired from the environment but can also move between anatomical sites within the same individual, thereby shaping the course of infection.

In a study published in Nature Communications, researchers examined how Pseudomonas aeruginosa spreads on and within hospitalized patients. The analysis showed that in more than half of the cases involving colonization of multiple organs, a pattern associated with a higher risk for sepsis was driven by internal bacterial translocation rather than repeated acquisition from the hospital environment.

Tracking Bacterial Spread

The ability of P aeruginosa to move from one body site to another has long been recognized. Previous reports have documented isolated cases of translocation, such as the spread from the intestine to the lungs, in patients requiring intensive care. However, it remains unclear how often the same bacterial strain disseminates within an individual and whether migration follows the preferred anatomical routes.

To address this question, the researchers analyzed metagenomic sequencing data from 256 hospitalized patients admitted to San Matteo Hospital, Pavia, Italy, during spring 2020. Routine nasal and rectal swabs were collected along with respiratory samples, including sputum and bronchoalveolar lavage, when indicated.

The final analysis included 320 samples from 84 patients, of whom 68 were sampled at multiple timepoints. Metagenomic sequencing of bacterial DNA combined with phylogenetic analysis was used to reconstruct the evolutionary relationships among the strains. A bacterial clone was defined as a group of samples differing by fewer than 100 single-nucleotide polymorphisms.

Internal Translocation Dominates

Overall, 67 of the 84 patients (81%) were colonized by the same P aeruginosa clone in all available samples. Among the patients with longitudinal sampling, 51 patient-specific clones were identified, of which 27 (53%) were detected at more than one body site.

A consistent pattern was observed in the nasal cavity. P aeruginosa was not detected in nasal swabs alone. When multiple samples were available, nasal colonization coincided with pulmonary colonization. This finding suggests that the upper airways do not serve as a stable reservoir but are transiently colonized through spillovers from other sites, most likely the lungs.

In contrast, 14 patients showed isolated rectal colonization only. Of these, 12 (86%) remained positive across multiple timepoints, indicating that the intestine provides a favorable niche for the long-term persistence of P aeruginosa.

To distinguish between internal spread and repeated environmental acquisition, investigators have developed a computer-simulated infection model. After 10,000 simulations, a purely environmental acquisition scenario was statistically incompatible with the observed data across all wards in the hospital setting (P < .001). The analysis indicated that 50% of within-host transfer best explained 75% of cases involving shared clones across body sites.

Direction and Clinical Implications

To infer the direction of bacterial movement, researchers have analyzed within-host genomic diversity and reconstructed phylogenetic relationships among bacterial clones using ancestral-state reconstruction. This analysis allowed the identification of the most likely initial body site of colonization and the probable pathways of spread between anatomical sites over time.

In most cases, the predominant route is from the lungs to the intestine. The researchers proposed swallowing of saliva as the potential origin of gut colonization for P aeruginosa. Although gastric acid represents a physiologic barrier, evidence suggests that swallowing saliva or sputum can lead to sustained intestinal colonization.

These findings suggest that colonization of the lower respiratory tract should be considered a risk factor for gut-derived sepsis in high-risk patients, particularly in the ICU.

Analysis of the genetic diversity within clones identified an additional concern. Among 31 nonsynonymous mutations, 16 (52%) occurred in genes associated with antimicrobial resistance, especially regulatory genes.

The rapid parallel emergence of antimicrobial resistance mutations across anatomical sites in P aeruginosa poses challenges for infection surveillance and prevention.

Predominant mutations in regulatory genes indicate that P aeruginosa adapts to selective hospital pressures by altering complex regulatory networks rather than individual effector genes.

This story was translated from Univadis Italy, part of the Medscape Professional Network.