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Yam, J. K. H.

Publications and source records attributed to Yam, J. K. H..

3 recordsLinked to original sources

Population dynamics and transcriptomic responses of Pseudomonas aeruginosa in a complex laboratory microbial community

Pseudomonas aeruginosa is one of the dominant species when it co-exists with many other bacterial species in diverse environments. To understand its physiology and interactions with co-existing bacterial species in different conditions, we established physiologically reproducible eighteen-species communities, and found that P. aeruginosa became the dominant species in mixed-species biofilm community but not in the planktonic community. P. aeruginosa H1 type VI secretion system was highly induced in the mixed-species biofilm community compare to its mono-species biofilm, which was further demonstrated to play a key role for P. aeruginosa to gain fitness over other bacterial species. In addition, the type IV pili and Psl exopolysaccharide were shown to be required for P. aeruginosa to compete with other bacterial species in the biofilm community. Our study showed that the physiology of P. aeruginosa is strongly affected by interspecies interactions, and both biofilm determinants and H1 type VI secretion system contribute to P. aeruginosa fitness over other species in complex biofilm communities.\n\nImportancePseudomonas aeruginosa usually coexists with different bacterial species in natural environment. However, systematic comparative characterization of P. aeruginosa in complex microbial communities with its mono-species communities is lacking. We constructed mixed-species planktonic and biofilm communities consisting P. aeruginosa and seventeen other bacterial species to study the physiology and interaction of P. aeruginosa in complex multiple-species community. A single molecule detection platform, NanoString nCounter(R) 16S rRNA array, was used to shown that P. aeruginosa can become the dominant species in the biofilm communities while not in the planktonic communities. Comparative transcriptomic analysis and fluorescence-based quantification further revealed that P. aeruginosa H1 type VI secretion system and biofilm determinants are both required for its fitness in mixed-species biofilm communities.

microbiology

Auranofin inhibits virulence in Pseudomonas aeruginosa

Pseudomonas aeruginosa is widely attributed as the leading cause of hospital-acquired infections. Due to intrinsic antibiotic resistance mechanisms and the ability to form biofilms, P. aeruginosa infections are challenging to treat. P. aeruginosa employs multiple virulence mechanisms to establish infections, many of which are controlled by the global virulence regulator Vfr. An attractive strategy to combat P. aeruginosa infections is thus the use of anti-virulence compounds. Here, we report the discovery that FDA-approved drug auranofin attenuates virulence in P. aeruginosa. We demonstrate that auranofin acts by targeting Vfr, which in turn leads to inhibition of quorum sensing (QS) and Type IV pili (TFP). Consistent with inhibition of QS and TFP expression, we show that auranofin attenuates biofilm maturation, and when used in combination with colistin, displays strong synergy in eradicating P. aeruginosa biofilms. Auranofin may have immediate applications as an anti-virulence drug against P. aeruginosa infections.

microbiology

Cyclic-di-GMP is required for corneal infection by Pseudomonas aeruginosa and modulates host immunity

Biofilms are extremely tolerant toward antimicrobial treatment and host immune clearance due to their distinct physiology and protection by extracellular polymeric substances. Bis-(3{acute}-5{acute})-cyclic dimeric guanosine monophosphate (c-di-GMP) is an essential messenger that regulates biofilm formation by a wide range of bacteria. However, there is a lack of physiological characterization of biofilms in vivo as well as the roles of c-di-GMP signaling in mediating host-biofilm interactions. Here, we employed dual RNA-Seq to characterize the host and pathogen transcriptomes during Pseudomonas aeruginosa infection using a mouse keratitis model. In vivo P. aeruginosa biofilms maintained a distinct physiology compared with in vitro P. aeruginosa biofilms, with enhanced virulence and iron uptake capacity. C-di-GMP synthesis was enhanced in P. aeruginosa cells in vivo, potentially due to down-regulation of the expression of several phosphodiesterases (e.g., DipA, NbdA). Increased intracellular c-di-GMP levels were required for long-term ocular colonization of P. aeruginosa and impaired host innate immunity.

microbiology