The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS

Abstract

Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 carries pathogenicity islands that are absent in PAO1, the presence or absence of specific gene clusters is not predictive of virulence. Here, we show that the virulent strain PA14 has an acquired mutation in the ladS gene. This mutation has a deleterious impact on biofilm, while it results in elevated type III secretion system (T3SS) activity and increased cytotoxicity towards mammalian cells. These phenotypes can be reverted by repairing the ladS mutation on the PA14 genome. The RetS/LadS/GacS signaling cascade is associated with virulence and the switch between acute and chronic infections. RetS is a sensor that down-regulates biofilm formation and up-regulates the T3SS. Mutations in retS are acquired in strains isolated from chronically infected cystic fibrosis patients and lead to hyperbiofilm formation and reduced cytotoxicity. Conversely, the LadS sensor promotes biofilm formation and represses the T3SS. We conclude that the ladS mutation is partly responsible for the high cytotoxicity of PA14, and our findings corroborate the central role of RetS and LadS in the switch between acute and chronic infections. Given the extensive use of the reference strain PA14 in infection and virulence models, the bias caused by the ladS mutation on the observed phenotypes will be crucial to consider in future research.

Determining Roles of Accessory Genes in Denitrification by Mutant Fitness Analyses

“…Thus, we propose that HsbR acts as an antisigma factor to RpoE, a sigma factor known to be involved in promoting transcription of genes required for proper maintenance and repair of periplasmic and outer membrane components (58). The only gene with a higher cofitness with hsbR (0.85) was a gene encoding a histidine kinase (Psest_0538), LadS, which is known to promote biofilm formation and to decrease cytotoxicity in P. aeruginosa (59). It appears that in P. stutzeri these two systems may be connected and that LadS participates in the same phospho-relay that activates HsbA.…”

Comparative Analyses of a Cystic Fibrosis Isolate of Bordetella bronchiseptica Reveal Differences in Important Pathogenic Phenotypes

“…Biofilm formation appears to be especially important for the persistence of bacteria in CF infections (61)(62)(63). Compared to RB50, T44625 displayed an enhanced ability for cellular aggregation and the formation of biofilms.…”

“…To our knowledge, this is the first report documenting hyperbiofilm formation by a clinical isolate of B. bronchiseptica. Strains isolated from chronically infected cystic fibrosis patients often acquire mutations in regulatory and other genes resulting in hyperbiofilm formation (63). It remains to be determined if similar mechanisms are operative in T44625.…”

Strain- and Substrate-Dependent Redox Mediator and Electricity Production by Pseudomonas aeruginosa

“…Genetically, strains PA14 and PAO1 are appreciably different, and they often show discernible physiological differences. PA14 has a slightly larger genome than PAO1 (ϳ6.54 and 6.26 MB, respectively), which contains several pathogenicity islands that are not present in PAO1 (34,35). The first pure culture evaluations of P. aeruginosa in BES have been performed with strain PA14 (9,27,32); however, this strain differs from the ones evolved in MFC microbial communities and might show different physiological and ecological behaviors.…”