Pyomelanin-producing Pseudomonas aeruginosa selected during chronic infections have a large chromosomal deletion which confers resistance to pyocins.
When bacterial lineages make the transition from free-living to permanent association with hosts, they can undergo massive gene losses, for which the selective forces within host tissues are unknown. We identified here melanogenic clinical isolates of Pseudomonas aeruginosa with large chromosomal deletions (66 to 270 kbp) and characterized them to investigate how they were selected. When compared with their wild-type parents, melanogenic mutants (i) exhibited a lower fitness in growth conditions found in human tissues, such as hyperosmolarity and presence of aminoglycoside antibiotics, (ii) narrowed their metabolic spectrum with a growth disadvantage with particular carbon sources, including aromatic amino acids and acyclic terpenes, suggesting a reduction of metabolic flexibility. Despite an impaired fitness in rich media, melanogenic mutants can inhibit their wild-type parents and compete with them in coculture. Surprisingly, melanogenic mutants became highly resistant to two intraspecific toxins, the S-pyocins AP41 and S1. Our results suggest that pyocins produced within a population of infecting P. aeruginosa may have selected for bacterial mutants that underwent massive gene losses and that were adapted to the life in diverse bacterial communities in the human host. Intraspecific interactions may therefore be an important factor driving the continuing evolution of pathogens during host infections.
UMR CNRS 6249, Chrono-environnement, Université de Bourgogne-Franche-Comté, Besançon, France. dhocquet@chu-besancon.fr.|Service d' Hygiène Hospitalière, Centre Hospitalier Régional Universitaire, Besançon, France. dhocquet@chu-besancon.fr.
Didier
D
Hocquet
UMR CNRS 6249, Chrono-environnement, Université de Bourgogne-Franche-Comté, Besançon, France.|Service d' Hygiène Hospitalière, Centre Hospitalier Régional Universitaire, Besançon, France.
Marie
M
Petitjean
Department of Microbiology, University of Washington, Seattle, WA, USA.
Laurence
L
Rohmer
UMR CNRS 6249, Chrono-environnement, Université de Bourgogne-Franche-Comté, Besançon, France.
Benoît
B
Valot
Department of Microbiology, University of Washington, Seattle, WA, USA.
Hemantha D
HD
Kulasekara
UMR CNRS 6249, Chrono-environnement, Université de Bourgogne-Franche-Comté, Besançon, France.|Service d' Hygiène Hospitalière, Centre Hospitalier Régional Universitaire, Besançon, France.
Elodie
E
Bedel
UMR CNRS 6249, Chrono-environnement, Université de Bourgogne-Franche-Comté, Besançon, France.|Service d' Hygiène Hospitalière, Centre Hospitalier Régional Universitaire, Besançon, France.
Xavier
X
Bertrand
Service de Bactériologie, Centre Hospitalier Régional Universitaire, Besançon, France.
Patrick
P
Plésiat
Département de Génétique et de Microbiologie, Centre Médical Universitaire, Genève, Suisse.
Thilo
T
Köhler
Service de Microbiologie, Centre Hospitalier Régional Universitaire, Nîmes, France.|UMR INSERM U1047, Université de Montpellier, Nîmes, France.
Alix
A
Pantel
Department of Microbiology, University of Washington, Seattle, WA, USA.
Michael A
MA
Jacobs
Department of Microbiology, University of Washington, Seattle, WA, USA.|Department of Pediatrics, University of Washington, Seattle, WA, USA.
Lucas R
LR
Hoffman
Department of Microbiology, University of Washington, Seattle, WA, USA.
Samuel I
SI
Miller
D002872:Chromosome Deletion; D002876:Chromosomes, Bacterial / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D011709:Pyocins / Q000494:pharmacology*
D008543:Melanins; D011709:Pyocins; C023793:pyomelanin