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      Bacterial Adaptation during Chronic Respiratory Infections

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          Abstract

          Chronic lung infections are associated with increased morbidity and mortality for individuals with underlying respiratory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The process of chronic colonisation allows pathogens to adapt over time to cope with changing selection pressures, co-infecting species and antimicrobial therapies. These adaptations can occur due to environmental pressures in the lung such as inflammatory responses, hypoxia, nutrient deficiency, osmolarity, low pH and antibiotic therapies. Phenotypic adaptations in bacterial pathogens from acute to chronic infection include, but are not limited to, antibiotic resistance, exopolysaccharide production (mucoidy), loss in motility, formation of small colony variants, increased mutation rate, quorum sensing and altered production of virulence factors associated with chronic infection. The evolution of Pseudomonas aeruginosa during chronic lung infection has been widely studied. More recently, the adaptations that other chronically colonising respiratory pathogens, including Staphylococcus aureus, Burkholderia cepacia complex and Haemophilus influenzae undergo during chronic infection have also been investigated. This review aims to examine the adaptations utilised by different bacterial pathogens to aid in their evolution from acute to chronic pathogens of the immunocompromised lung including CF and COPD.

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          Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective.

          The airways of patients with cystic fibrosis (CF) are nearly always infected with many different microorganisms. This environment offers warm, humid and nutrient-rich conditions, but is also stressful owing to frequent antibiotic therapy and the host immune response. Pseudomonas aeruginosa is commonly isolated from the airways of patients with CF, where it most often establishes chronic infections that usually persist for the rest of the lives of the patients. This bacterium is a major cause of mortality and morbidity and has therefore been studied intensely. Here, we discuss how P. aeruginosa evolves from a state of early, recurrent intermittent colonization of the airways of patients with CF to a chronic infection state, and how this process offers opportunities to study bacterial evolution in natural environments. We believe that such studies are valuable not only for our understanding of bacterial evolution but also for the future development of new therapeutic strategies to treat severe chronic infections.
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            Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia.

            Respiratory infections with Pseudomonas aeruginosa and Burkholderia cepacia play a major role in the pathogenesis of cystic fibrosis (CF). This review summarizes the latest advances in understanding host-pathogen interactions in CF with an emphasis on the role and control of conversion to mucoidy in P. aeruginosa, a phenomenon epitomizing the adaptation of this opportunistic pathogen to the chronic chourse of infection in CF, and on the innate resistance to antibiotics of B. cepacia, person-to-person spread, and sometimes rapidly fatal disease caused by this organism. While understanding the mechanism of conversion to mucoidy in P. aeruginosa has progressed to the point where this phenomenon has evolved into a model system for studying bacterial stress response in microbial pathogenesis, the more recent challenge with B. cepacia, which has emerged as a potent bona fide CF pathogen, is discussed in the context of clinical issues, taxonomy, transmission, and potential modes of pathogenicity.
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              Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection

              Staphylococcus aureus is a frequent cause for serious, chronic and therapy-refractive infections in spite of susceptibility to antibiotics in vitro. In chronic infections, altered bacterial phenotypes, such as small colony variants (SCVs), have been found. Yet, it is largely unclear whether the ability to interconvert from the wild-type to the SCV phenotype is only a rare clinical and/or just laboratory phenomenon or is essential to sustain an infection. Here, we performed different long-term in vitro and in vivo infection models with S. aureus and we show that viable bacteria can persist within host cells and/or tissues for several weeks. Persistence induced bacterial phenotypic diversity, including SCV phenotypes, accompanied by changes in virulence factor expression and auxotrophism. However, the recovered SCV phenotypes were highly dynamic and rapidly reverted to the fully virulent wild-type form when leaving the intracellular location and infecting new cells. Our findings demonstrate that bacterial phenotype switching is an integral part of the infection process that enables the bacteria to hide inside host cells, which can be a reservoir for chronic and therapy-refractive infections.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                02 March 2015
                March 2015
                : 4
                : 1
                : 66-89
                Affiliations
                Centre of Microbial Host Interactions, Institute of Technology Tallaght, Dublin 24, Ireland; E-Mail: Louise.cullen@ 123456postgrad.ittdublin.ie
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: Siobhan.mcclean@ 123456ittdublin.ie ; Tel.: +353-1-4042794.
                Article
                pathogens-04-00066
                10.3390/pathogens4010066
                4384073
                25738646
                f8369f7f-7d63-4594-a816-a381ba5fb6bd
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 December 2014
                : 25 February 2015
                Categories
                Review

                respiratory pathogens,bacterial adaptation,chronic infection,evolution,diversification,cystic fibrosis,chronic obstructive pulmonary disease (copd)

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