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Cooperativity between Stenotrophomonas maltophilia and Pseudomonas aeruginosa during Polymicrobial Airway Infections.

ABSTRACT: Stenotrophomonas maltophilia is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. S. maltophilia is increasingly observed in patient sputa in cystic fibrosis (CF), and while existing epidemiology indicates that patients with S. maltophilia have poorer diagnoses, its clinical significance remains unclear. Moreover, as multidrug resistance is common among S. maltophilia isolates, treatment options for these infections may be limited. Here, we investigated the pathogenicity of S. maltophilia alone and during polymicrobial infection with Pseudomonas aeruginosa Colonization, persistence, and virulence of S. maltophilia were assessed in experimental respiratory infections of mice. The results of this study indicate that S. maltophilia transiently colonizes the lung accompanied by significant weight loss and immune cell infiltration and the expression of early inflammatory markers, including interleukin 6 (IL-6), IL-1?, and tumor necrosis factor alpha (TNF-?). Importantly, polymicrobial infection with P. aeruginosa elicited significantly higher S. maltophilia counts in bronchoalveolar lavages and lung tissue homogenates. This increase in bacterial load was directly correlated with the density of the P. aeruginosa population and required viable P. aeruginosa bacteria. Microscopic analysis of biofilms formed in vitro revealed that S. maltophilia formed well-integrated biofilms with P. aeruginosa, and these organisms colocalize in the lung during dual-species infection. Based on these results, we conclude that active cellular processes by P. aeruginosa afford a significant benefit to S. maltophilia during polymicrobial infections. Furthermore, these results indicate that S. maltophilia may have clinical significance in respiratory infections.

SUBMITTER: McDaniel MS

PROVIDER: S-EPMC7093137 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Cooperativity between Stenotrophomonas maltophilia and Pseudomonas aeruginosa during Polymicrobial Airway Infections.

McDaniel Melissa S MS Schoeb Trenton T Swords W Edward WE

Infection and immunity 20200323 4

Stenotrophomonas maltophilia is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. S. maltophilia is increasingly observed in patient sputa in cystic fibrosis (CF), and while existing epidemiology indicates that patients with S. maltophilia have poorer diagnoses, its clinical significance remains unclear. Moreover, as multidrug resistance is common among S. maltophilia isolates, treatment options for t ...[more]

PMID: 31932329

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Project description:Stenotrophomonas maltophilia is an emerging opportunistic respiratory pathogen in people with cystic fibrosis (CF). S. maltophilia is frequently observed in polymicrobial infections, and we have previously shown that Pseudomonas aeruginosa promotes colonization and persistence of S. maltophilia in mouse respiratory infections. In this study, we used host and bacterial RNA sequencing to further understand the molecular underpinnings of this interaction. To evaluate S. maltophilia transcript profiles, we used a recently described method for selective capture of bacterial mRNA transcripts with strain-specific RNA probes. We found that factors associated with the type IV pilus, including the histidine kinase subunit of a chemotactic two-component signaling system (chpA), had increased transcript levels during dual-species infection. Using immortalized CF respiratory epithelial cells, we found that infection with P. aeruginosa increases adherence of S. maltophilia, at least in part due to disruption of epithelial tight junctions. In contrast, an isogenic S. maltophilia chpA mutant strain lacked cooperative adherence to CF epithelia and decreased bacterial burden in vivo in dual-species infections with P. aeruginosa. Similarly, P. aeruginosa lacking elastase (lasB) failed to promote S. maltophilia adherence or bacterial colonization and persistence in vivo. Based on these results, we propose that disruption of lung tissue integrity by P. aeruginosa facilitates adherence of S. maltophilia to the lung epithelia, likely in a type IV pilus-dependent manner. These data lend insight into S. maltophilia colonization and persistence in people in later stages of CF disease and may have implications for interactions with other bacterial opportunists. IMPORTANCE Despite advances in treatment options for people with CF, complications of bacterial infections remain the greatest driver of morbidity and mortality in this patient population. These infections often involve more than one bacterial pathogen, and our understanding of how interspecies interactions impact disease progression is lacking. Previous work in our lab found that two CF pathogens, Stenotrophomonas maltophilia and Pseudomonas aeruginosa, can work together in the lung to cause more severe infection. In the present study, we found that infection with P. aeruginosa promotes persistence of S. maltophilia by interfering with epithelial barrier integrity. Depolarization of the epithelial cell layer by P. aeruginosa-secreted elastase increased S. maltophilia adherence, likely in a type IV pilus-dependent manner. Ultimately, this work sheds light on the molecular mechanisms governing an important multispecies interaction seen in pulmonary diseases such as CF.

Project description:The Pseudomonas aeruginosa bacterium is a common pathogen of cystic fibrosis (CF) patients due to its ability to evolve resistance to antibiotics during treatments. While P. aeruginosa resistance evolution is well-characterized in monocultures, it is less well-understood in polymicrobial CF infections. Here, we investigated how exposure to ciprofloxacin, colistin, or tobramycin antibiotics, administered at sub-minimum inhibitory concentration (MIC) doses, both alone and in combination, shaped the tolerance evolution of P. aeruginosa (PAO1 lab and clinical CF LESB58 strains) in the absence and presence of a commonly co-occurring species, Stenotrophomonas maltophilia. The increases in antibiotic tolerances were primarily driven by the presence of that antibiotic in the treatment. We observed a reciprocal cross-tolerance between ciprofloxacin and tobramycin, and, when combined, the selected antibiotics increased the MICs for all of the antibiotics. Though the presence of S. maltophilia did not affect the tolerance or the MIC evolution, it drove P. aeruginosa into extinction more frequently in the presence of tobramycin due to its relatively greater innate tobramycin tolerance. In contrast, P. aeruginosa dominated and drove S. maltophilia extinct in most other treatments. Together, our findings suggest that besides driving high-level antibiotic tolerance evolution, sub-MIC antibiotic exposure can alter competitive bacterial interactions, leading to target pathogen extinctions in multispecies communities. IMPORTANCE Cystic fibrosis (CF) is a genetic condition that results in thick mucus secretions in the lungs that are susceptible to chronic bacterial infections. The bacterial pathogen Pseudomonas aeruginosa is often associated with morbidity in CF and is difficult to treat due to its high resistance to antibiotics. The resistance evolution of Pseudomonas aeruginosa is poorly understood in polymicrobial infections that are typical of CF. To study this, we exposed P. aeruginosa to sublethal concentrations of ciprofloxacin, colistin, or tobramycin antibiotics in the absence and presence of a commonly co-occurring CF species, Stenotrophomonas maltophilia. We found that low-level antibiotic concentrations selected for high-level antibiotic resistance. While P. aeruginosa dominated in most antibiotic treatments, S. maltophilia drove it into extinction in the presence of tobramycin due to an innately higher tobramycin resistance. Our findings suggest that, besides driving high-level antibiotic tolerance evolution, sublethal antibiotic exposure can magnify competition in bacterial communities, which can lead to target pathogen extinctions in multispecies communities.

Dataset Information

Cooperativity between Stenotrophomonas maltophilia and Pseudomonas aeruginosa during Polymicrobial Airway Infections.

Publications

Cooperativity between Stenotrophomonas maltophilia and Pseudomonas aeruginosa during Polymicrobial Airway Infections.

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