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      From genotype to phenotype: adaptations of Pseudomonas aeruginosa to the cystic fibrosis environment

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          Abstract

          Pseudomonas aeruginosa is one of the main microbial species colonizing the lungs of cystic fibrosis patients and is responsible for the decline in respiratory function. Despite the hostile pulmonary environment, P. aeruginosa is able to establish chronic infections thanks to its strong adaptive capacity. Various longitudinal studies have attempted to compare the strains of early infection with the adapted strains of chronic infection. Thanks to new ‘-omics’ techniques, convergent genetic mutations, as well as transcriptomic and proteomic dysregulations have been identified. As a consequence of this evolution, the adapted strains of P. aeruginosa have particular phenotypes that promote persistent infection.

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          Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

          Pseudomonas aeruginosa is an opportunistic pathogen affecting immunocompromised patients. It is known as the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and as one of the leading causes of nosocomial infections. Due to a range of mechanisms for adaptation, survival and resistance to multiple classes of antibiotics, infections by P. aeruginosa strains can be life-threatening and it is emerging worldwide as public health threat. This review highlights the diversity of mechanisms by which P. aeruginosa promotes its survival and persistence in various environments and particularly at different stages of pathogenesis. We will review the importance and complexity of regulatory networks and genotypic-phenotypic variations known as adaptive radiation by which P. aeruginosa adjusts physiological processes for adaptation and survival in response to environmental cues and stresses. Accordingly, we will review the central regulatory role of quorum sensing and signaling systems by nucleotide-based second messengers resulting in different lifestyles of P. aeruginosa. Furthermore, various regulatory proteins will be discussed which form a plethora of controlling systems acting at transcriptional level for timely expression of genes enabling rapid responses to external stimuli and unfavorable conditions. Antibiotic resistance is a natural trait for P. aeruginosa and multiple mechanisms underlying different forms of antibiotic resistance will be discussed here. The importance of each mechanism in conferring resistance to various antipseudomonal antibiotics and their prevalence in clinical strains will be described. The underlying principles for acquiring resistance leading pan-drug resistant strains will be summarized. A future outlook emphasizes the need for collaborative international multidisciplinary efforts to translate current knowledge into strategies to prevent and treat P. aeruginosa infections while reducing the rate of antibiotic resistance and avoiding the spreading of resistant strains.
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            Cooperation and conflict in quorum-sensing bacterial populations.

            It has been suggested that bacterial cells communicate by releasing and sensing small diffusible signal molecules in a process commonly known as quorum sensing (QS). It is generally assumed that QS is used to coordinate cooperative behaviours at the population level. However, evolutionary theory predicts that individuals who communicate and cooperate can be exploited. Here we examine the social evolution of QS experimentally in the opportunistic pathogen Pseudomonas aeruginosa, and show that although QS can provide a benefit at the group level, exploitative individuals can avoid the cost of producing the QS signal or of performing the cooperative behaviour that is coordinated by QS, and can therefore spread. We also show that a solution to the problem of exploitation is kin selection, if interacting bacterial cells tend to be close relatives. These results show that the problem of exploitation, which has been the focus of considerable attention in animal communication, also arises in bacteria.
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              Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections

              Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification.
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                Author and article information

                Journal
                Microb Genom
                Microb Genom
                mgen
                mgen
                Microbial Genomics
                Microbiology Society
                2057-5858
                March 2021
                2 February 2021
                2 February 2021
                : 7
                : 3
                : mgen000513
                Affiliations
                [ 1] departmentCIRI – Centre International de Recherche en Infectiologie , Université de Lyon/Inserm U1111/Université Claude Bernard Lyon 1/CNRS UMR5308/ENS de Lyon , Lyon, France
                [ 2] departmentCentre National de Référence des Staphylocoques , Hospices Civils de Lyon , Lyon, France
                [ 3] departmentInstitut des Agents Infectieux , Hospices Civils de Lyon , Lyon, France
                Author notes
                *Correspondence: Karen Moreau, karen.moreau@ 123456univ-lyon1.fr
                Author information
                https://orcid.org/0000-0003-1335-8901
                https://orcid.org/0000-0001-9412-7106
                https://orcid.org/0000-0001-6297-3543
                Article
                000513
                10.1099/mgen.0.000513
                8190622
                33529147
                091a223e-dad2-4b7a-9a66-e9744d564258
                © 2021 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License.

                History
                : 30 July 2020
                : 21 December 2020
                Funding
                Funded by: Association Gregory Lemarchal
                Award Recipient : KarenMoreau
                Funded by: Association Vaincre la Mucoviscidose
                Award Recipient : KarenMoreau
                Funded by: Fondation Innovations en Infectiologie
                Award Recipient : KarenMoreau
                Funded by: FRM
                Award ID: ECO20170637499
                Award Recipient : LauraCamus
                Categories
                Reviews
                Pathogens and Epidemiology
                Custom metadata
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                adaptation,cystic fibrosis,genomic,phenotype,pseudomonas aeruginosa

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