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2017 ; 8
(2
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with
Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection
#MMPMID28325763
Limoli DH
; Whitfield GB
; Kitao T
; Ivey ML
; Davis MR Jr
; Grahl N
; Hogan DA
; Rahme LG
; Howell PL
; O'Toole GA
; Goldberg JB
mBio
2017[Mar]; 8
(2
): ä PMID28325763
show ga
While complex intra- and interspecies microbial community dynamics are apparent
during chronic infections and likely alter patient health outcomes, our
understanding of these interactions is currently limited. For example,
Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the
lungs of patients with cystic fibrosis (CF), yet these organisms compete under
laboratory conditions. Recent observations that coinfection correlates with
decreased health outcomes necessitate we develop a greater understanding of these
interbacterial interactions. In this study, we tested the hypothesis that
P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during
infection. We compared competitive interactions of P. aeruginosa and S. aureus
isolates from mono- or coinfected CF patients employing in vitro coculture
models. P. aeruginosa isolates from monoinfected patients were more competitive
toward S. aureus than P. aeruginosa isolates from coinfected patients. We also
observed that the least competitive P. aeruginosa isolates possessed a mucoid
phenotype. Mucoidy occurs upon constitutive activation of the sigma factor
AlgT/U, which regulates synthesis of the polysaccharide alginate and dozens of
other secreted factors, including some previously described to kill S. aureus
Here, we show that production of alginate in mucoid strains is sufficient to
inhibit anti-S. aureus activity independent of activation of the AlgT regulon.
Alginate reduces production of siderophores, 2-heptyl-4-hydroxyquinolone-N-oxide
(HQNO), and rhamnolipids-each required for efficient killing of S. aureus These
studies demonstrate alginate overproduction may be an important factor driving
P. aeruginosa coinfection with S. aureusIMPORTANCE Numerous deep-sequencing
studies have revealed the microbial communities present during respiratory
infections in cystic fibrosis (CF) patients are diverse, complex, and dynamic. We
now face the challenge of determining the influence of these community dynamics
on patient health outcomes and identifying candidate targets to modulate these
interactions. We make progress toward this goal by determining that the
polysaccharide alginate produced by mucoid strains of P. aeruginosa is sufficient
to inhibit multiple secreted antimicrobial agents produced by this organism.
Importantly, these secreted factors are required to outcompete S. aureus, when
the microbes are grown in coculture; thus we propose a mechanism whereby mucoid
P. aeruginosa can coexist with S. aureus Finally, the approach used here can
serve as a platform to investigate the interactions among other CF pathogens.