Manipulating virulence factor availability can have complex consequences for infections

Weigert, Michael; Ross‐Gillespie, Adin; Leinweber, Anne; Pessi, Gabriella; Brown, Sam P.; Kümmerli, Rolf

doi:10.1111/eva.12431

Cited by 25 publications

(14 citation statements)

References 71 publications

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“…The link between pyoverdine and virulence has been clearly established in many contexts, including in C. elegans Liquid Killing and in murine infections. However, recent studies in a Galleria mellonella infection model demonstrated a more complicated relationship between pyoverdine and pathogenesis (Weigert et al, 2017). The addition of exogenous pyoverdine at low concentrations seemed to attenuate pathogen virulence.…”

Section: Discussionmentioning

confidence: 99%

Pyoverdine-Dependent Virulence of Pseudomonas aeruginosa Isolates From Cystic Fibrosis Patients

et al. 2019

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The development of therapies that modulate or prevent pathogen virulence may be a key strategy for circumventing antimicrobial resistance. Toward that end, we examined the production of pyoverdine, a key virulence determinant, in ∼70 Pseudomonas aeruginosa isolates from pediatric cystic fibrosis patients. Pyoverdine production was heterogeneous and showed a clear correlation with pathogenicity in Caenorhabditis elegans and an acute murine pneumonia model. Examination showed pyoverdine accumulation in host tissues, including extrapharyngeal tissues of C. elegans and lung tissues of mice, where accumulation correlated with host death. Many of the isolates tested were resistant to multiple antimicrobials, so we assayed the ability of pyoverdine inhibitors to mitigate virulence and rescue pyoverdine-mediated host pathology. Representatives from three different classes of pyoverdine inhibitors (gallium, fluoropyrimidines, and LK11) significantly improved survival. Our findings highlight the utility of targeting virulence factors in general, and pyoverdine in particular, as a promising method to control bacterial pathogenesis as the utility of antimicrobials continues to diminish.

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Section: Discussionmentioning

confidence: 99%

Pyoverdine-Dependent Virulence of Pseudomonas aeruginosa Isolates From Cystic Fibrosis Patients

et al. 2019

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“…This is easily measured when virulence and growth are correlated and when symbionts can be distinguished in a multiple infection 8 . However, virulence is not always related to symbiont growth, as assumed by most theoretical models, but might be due to immunopathology 73 , 74 . In such cases, symbionts in a multiple infection with facilitation might interact in such a way that virulence does not correspond to the sum of the virulence measured in each single infection.…”

Section: Ecological and Evolutionary Consequences Of Facilitationmentioning

confidence: 99%

Ecology and evolution of facilitation among symbionts

Zélé¹,

Magalhães²,

Kéfi³

et al. 2018

Nat Commun

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Facilitation occurs when one species positively impacts the fitness of another, and has predominantly been studied in free-living species like plants. Facilitation can also occur among symbiont (mutualistic or parasitic) species or strains, but equivalent studies are scarce. To advance an integrated view of the effect of facilitation on symbiont ecology and evolution, we review empirical evidence and their underlying mechanisms, explore the factors favouring its emergence, and discuss its consequences for virulence and transmission. We argue that the facilitation concept can improve understanding of the evolutionary forces shaping symbiont communities and their effects on hosts.

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“…This positive feedback, triggered by successful iron uptake, is opposed by a negative feedback operated by Fur (ferric uptake regulator), which silences pyoverdine synthesis once enough iron has been taken up (16,44). Our results can be interpreted in the light of these feedbacks, given that the relative strength of the opposing feedbacks determines the resulting pyoverdine investment levels (45). For example, producer micro-colonies reach higher cell densities in mono-compared to mixed cultures (figure 3, after 3h: 13.2 ± 2.3 versus 6.7 ± 1.3 cells; after 5h: 122.7 ± 17.9 versus 55.0 ± 8.1 cells, respectively).…”

Section: Discussionmentioning

confidence: 80%

The physical boundaries of public goods cooperation between surface-attached bacterial cells

Weigert

Kümmerli

2017

Proc. R. Soc. B.

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Bacteria secrete a variety of compounds important for nutrient scavenging, competition mediation and infection establishment. While there is a general consensus that secreted compounds can be shared and therefore have social consequences for the bacterial collective, we know little about the physical limits of such bacterial social interactions. Here, we address this issue by studying the sharing of iron-scavenging siderophores between surface-attached microcolonies of the bacterium Pseudomonas aeruginosa. Using single-cell fluorescent microscopy, we show that siderophores, secreted by producers, quickly reach non-producers within a range of 100 µm, and significantly boost their fitness. Producers in turn respond to variation in sharing efficiency by adjusting their pyoverdine investment levels. These social effects wane with larger cell-to-cell distances and on hard surfaces. Thus, our findings reveal the boundaries of compound sharing, and show that sharing is particularly relevant between nearby yet physically separated bacteria on soft surfaces, matching realistic natural conditions such as those encountered in soft tissue infections.

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Manipulating virulence factor availability can have complex consequences for infections

Cited by 25 publications

References 71 publications

Pyoverdine-Dependent Virulence of Pseudomonas aeruginosa Isolates From Cystic Fibrosis Patients

Pyoverdine-Dependent Virulence of Pseudomonas aeruginosa Isolates From Cystic Fibrosis Patients

Ecology and evolution of facilitation among symbionts

The physical boundaries of public goods cooperation between surface-attached bacterial cells

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