Harnessing bacterial interactions to manage infections: a review on the opportunistic pathogen Pseudomonas aeruginosa as a case example

Rezzoagli, Chiara; Granato, Elisa T.; Kümmerli, Rolf

doi:10.1099/jmm.0.001134

Cited by 36 publications

(41 citation statements)

References 164 publications

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“…Even with this limitation, our results support the conclusion that subgroup D is a nutritional generalist relative to other Gardnerella spp.. Most of the ecological studies that have been performed to date to elucidate mechanisms shaping the assembly of bacterial communities have included either environmental bacterial species or well-characterized model organisms [13,15,26,33,38,[43][44][45][46][47]. There are understandably fewer studies that focus on interactions among host-associated microbiota [48,49].…”

Section: Subgroup D Is a Nutritional Generalist Relative To Subgroup supporting

confidence: 73%

A generalist lifestyle allows rareGardnerellaspp. to persist at low levels in the vaginal microbiome

Khan

Vancuren

Hill

2020

Preprint

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Gardnerella spp. are considered a hallmark of bacterial vaginosis, a dysbiosis of the vaginal microbiome. There are four cpn60 sequence-based subgroups within the genus (A, B, C, and D), and thirteen genome species have been defined recently. Gardnerella spp. co-occur in the vaginal microbiome with varying abundance, and these patterns are shaped by a resource-dependent, exploitative competition, which affects the growth rate of subgroup A, B, and C negatively. The growth rate of rarely abundant subgroup D, however, increases with the increasing number of competitors, negatively affecting the growth rate of others. We hypothesized that a nutritional generalist lifestyle and minimal niche overlap with the other, more abundant Gardnerella spp. facilitate the maintenance of subgroup D in the vaginal microbiome through negative-frequency dependent selection. Using 40 whole genome sequences from isolates representing all four subgroups we found that they could be distinguished based on content of their predicted proteomes. Proteins associated with carbohydrate and amino acid uptake and metabolism were significant contributors to the separation of subgroups. Subgroup D isolates had significantly more of their proteins assigned to amino acid metabolism than the other subgroups. Subgroup D isolates were also significantly different from others in terms of number and type of carbon sources utilized in a phenotypic assay, while the other three could not be distinguished. Overall, the results suggest that a generalist lifestyle and lack of niche overlap with other Gardnerella spp. leads to subgroup D being favoured by negative-frequency dependent selection in the vaginal microbiome.

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Section: Subgroup D Is a Nutritional Generalist Relative To Subgroup supporting

confidence: 73%

A generalist lifestyle allows rareGardnerellaspp. to persist at low levels in the vaginal microbiome

Khan

Vancuren

Hill

2020

Preprint

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“…aeruginosa is one of the ESKAPE pathogens with multidrug resistant strains spreading worldwide and infections becoming increasingly difficult to treat [19,20]. In addition to its clinical relevance, P. aeruginosa has become a model system for antivirulence research [21]. Several antivirulence compounds targeting either the species' quorum sensing (QS) [22][23][24] or siderophore-mediated iron uptake systems [25][26][27][28] have been proposed.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to its clinical relevance, P . aeruginosa has become a model system for antivirulence research [ 21 ]. Several antivirulence compounds targeting either the species’ quorum sensing (QS) [ 22 – 24 ] or siderophore-mediated iron uptake systems [ 25 – 28 ] have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa

et al. 2020

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Antibiotics are losing efficacy due to the rapid evolution and spread of resistance. Treatments targeting bacterial virulence factors have been considered as alternatives because they target virulence instead of pathogen viability, and should therefore exert weaker selection for resistance than conventional antibiotics. However, antivirulence treatments rarely clear infections, which compromises their clinical applications. Here, we explore the potential of combining antivirulence drugs with antibiotics against the opportunistic human pathogen Pseudomonas aeruginosa. We combined two antivirulence compounds (gallium, a siderophore quencher, and furanone C-30, a quorum sensing [QS] inhibitor) together with four clinically relevant antibiotics (ciprofloxacin, colistin, meropenem, tobramycin) in 9×9 drug concentration matrices. We found that drug-interaction patterns were concentration dependent, with promising levels of synergies occurring at intermediate drug concentrations for certain drug pairs. We then tested whether antivirulence compounds are potent adjuvants, especially when treating antibiotic resistant (AtbR) clones. We found that the addition of antivirulence compounds to antibiotics could restore growth inhibition for most AtbR clones, and even abrogate or reverse selection for resistance in five drug combination cases. Molecular analyses suggest that selection against resistant clones occurs when resistance mechanisms involve restoration of protein synthesis, but not when efflux pumps are up-regulated. Altogether, our work provides a first systematic analysis of antivirulenceantibiotic combinatorial treatments and suggests that such combinations have the potential to be both effective in treating infections and in limiting the spread of antibiotic resistance.

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“…Experimental microbial evolution (EME) studies have found that biofilm populations select for different mutations than those seen in planktonic growth, and the greater environmental structure of the biofilm produces increased genetic diversity 3,4,5,6,7,8,5,8,4,9 . Despite this process of diversification, replicate populations propagated in both biofilm and planktonic conditions exhibit high levels of both phenotypic and genetic parallelism, suggesting some measure of predictability within the same environment 10,7,11,12,13,14,15 . However, we still have much to learn about how the biofilm life cycle influences evolutionary dynamics and processes, including the relative roles of mutation and selection, and whether biofilm growth becomes the dominant selective force relative to other stresses like nutrient limitation or external toxins.…”

Section: Introductionmentioning

confidence: 99%

Polygenic adaptation, clonal interference, and the evolution of mutators in experimentalPseudomonas aeruginosapopulations

Harris

Flynn

Cooper

2021

Preprint

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In bacterial populations, switches in lifestyle from motile, planktonic growth to surface-associated biofilm is associated with persistence both in the environment and infections. Studies have identified the first steps of adaptation to biofilm growth but have yet to replicate the extensive genetic diversity observed in chronic infections or in the natural environment. We conducted an evolution experiment with Pseudomonas aeruginosa PA14 in growth media that promotes biofilm formation for 90 days in either planktonic culture or in a biofilm bead model. Surprisingly, all populations evolved extensive genetic diversity with hundreds of mutations maintained at intermediate frequencies, while fixation events were rare. Instead of the expected few beneficial mutations rising in frequency through successive sweeps, we observe a remarkable 40 genes with parallel mutations spanning both environments and often on coexisting genotypes within a population. Additionally, the evolution of mutator genotypes (mutS or mutL mutator alleles) that rise to high frequencies in as little as 25 days contribute to the extensive genetic variation and strong clonal interference. Parallelism in several transporters (including pitA, pntB, nosD, and pchF) indicate probable adaptation to the arginine media that becomes highly alkaline during growth, whereas genes involved in signal transduction (including gacS, aer2, bdlA, and PA14_71750) reflect likely adaptations to biofilm-inducing conditions. This experiment shows how extensive genetic and phenotypic diversity can arise and persist in microbial populations despite strong selection that would normally purge diversity.

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Harnessing bacterial interactions to manage infections: a review on the opportunistic pathogen Pseudomonas aeruginosa as a case example

Cited by 36 publications

References 164 publications

A generalist lifestyle allows rareGardnerellaspp. to persist at low levels in the vaginal microbiome

A generalist lifestyle allows rareGardnerellaspp. to persist at low levels in the vaginal microbiome

Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa

Polygenic adaptation, clonal interference, and the evolution of mutators in experimentalPseudomonas aeruginosapopulations

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