Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial

Piewngam, Pipat; Khongthong, Sunisa; Roekngam, Natthrit; Theapparat, Yongyuth; Sunpaweravong, Somkiat; Faroongsarng, Damrongsak; Otto, Michael

doi:10.1016/s2666-5247(22)00322-6

Cited by 60 publications

(25 citation statements)

References 29 publications

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Section: Discussionmentioning

confidence: 85%

“…In line with these findings, S. aureus QS signal-blind mutants possess a significant survival advantage in vivo (119), and a separate study reported that S. aureus strains that caused the most severe disease were the least toxic due, in part, to within-host fitness differences(120). Despite previous clinical trials showing a reduction in S. aureus colonization after supplementation with a B. subtilis probiotic(34), future studies should aim to investigate how residual S. aureus populations evolve in these host-associated systems. Still, our study provides the first evidence that long-term exposure to a collection of probiotic derived compounds harboring QSI activity, like those found in B. subtilis 6D1 CFE, can inhibit multiple S. aureus virulence mechanisms without increasing resistance to antibiotics.…”

Section: Discussionmentioning

confidence: 99%

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Bacillus subtilismaintains antibiofilm activity againstStaphylococcus aureusfollowing adaptive laboratory evolution

Leistikow,

Solis,

Khaled

et al. 2023

Preprint

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Quorum sensing interference has been touted as an ideal mechanism for the development of new anti-virulence therapies. Recent work has establishedBacillus subtilis6D1, a Gram-positive spore forming bacterium with probiotic qualities, produces metabolites that inhibitStaphylococcus aureusvirulence and biofilm formation via quorum sensing interference. However, it remains unknown how long-term exposure to these molecules driveS. aureusadaptation and evolution.S. aureusplanktonic cells and biofilms were propagated in the presence ofB. subtilis6D1 cell free extracts (CFE) for ~73 generations. Fitness, virulence, and antibiotic resistance assays of the ancestor and all evolved lineages revealed the emergence of treatment and lifestyle associated ecological traits. Compared to the ancestor and media-evolved lineages,S. aureuslineages evolved in the presence ofB. subtilis6D1 CFE were less competitive in a biofilm and exhibited increased phenotypic sensitivity to multiple antibiotics. Notably,B. subtilis6D1 CFE maintained its ability to inhibitS. aureusbiofilm growth and disassemble mature biofilm in all evolved lineages.S. aureuspopulations propagated in the presence of CFE acquired missense mutations in genes associated with plasmid-borne efflux systems and RNA polymerase. Furthermore, CFE-evolved lineages did not develop mutations in both competence and drug resistance pathways found in similarly evolved control lineages. Our data suggest long-term exposure to biofilm inhibitory molecules, like those produced byB. subtilis6D1, can reduceS. aureus’fitness in a biofilm and increase sensitivity to multiple antibiotics.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Bacillus subtilismaintains antibiofilm activity againstStaphylococcus aureusfollowing adaptive laboratory evolution

Leistikow,

Solis,

Khaled

et al. 2023

Preprint

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“…Despite some caution in the staphylococcal field to use “non-infectious” strains to control infectious strains, which is based on the problems surrounding the early use of S. aureus strain 502A for that purpose [ 91 ], recent studies on Agr interference to control colonization of S. aureus by coagulase-negative staphylococci may be useful in that regard, especially for the control of skin infections such as atopic dermatitis [ 63 , 92 ]. Furthermore, Bacillus species have been found to produce Agr quorum-quenching agents that when orally administered block S. aureus colonization in the intestine in mice [ 27 ], and as recently shown in a human trial efficiently reduce overall S. aureus colonization in humans [ 93 ].…”

Section: Probiotic/bacterial Interaction and Antibody-based Approachesmentioning

confidence: 99%

Critical Assessment of the Prospects of Quorum-Quenching Therapy for Staphylococcus aureus Infection

Otto

2023

IJMS

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Staphylococcus aureus is an important pathogen that causes a high number of infections and is one of the leading causes of death in hospitalized patients. Widespread antibiotic resistance such as in methicillin-resistant S. aureus (MRSA) has prompted research into potential anti-virulence-targeted approaches. Targeting the S. aureus accessory gene regulator (Agr) quorum-sensing system, a master regulator of virulence, is the most frequently proposed anti-virulence strategy for S. aureus. While much effort has been put into the discovery and screening for Agr inhibitory compounds, in vivo analysis of their efficacy in animal infection models is still rare and reveals various shortcomings and problems. These include (i) an almost exclusive focus on topical skin infection models, (ii) technical problems that leave doubt as to whether observed in vivo effects are due to quorum-quenching, and (iii) the discovery of counterproductive biofilm-increasing effects. Furthermore, potentially because of the latter, invasive S. aureus infection is associated with Agr dysfunctionality. Altogether, the potential of Agr inhibitory drugs is nowadays seen with low enthusiasm given the failure to provide sufficient in vivo evidence for their potential after more than two decades since the initiation of such efforts. However, current Agr inhibition-based probiotic approaches may lead to a new application of Agr inhibition strategies in preventing S. aureus infections by targeting colonization or for otherwise difficult-to-treat skin infections such as atopic dermatitis.

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“…[3][4][5] In the field of medicine and health, increasing infectious diseases such as diarrhea and pneumonia are getting harder to treat. 6,7 According to the World Health Organization, almost all the pathogens that cause infectious deaths show drug resistance to antibiotics. [8][9][10] In the animal husbandry field, antibiotics are excessively and inappropriately used to prevent and treat infectious diseases of livestock and poultry, also leading to serious drug resistance.…”

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confidence: 99%

Insights into the eradication of drug resistant Staphylococcus aureus via compound 6-nitrobenzo[cd]indole-2(1H)-ketone

Qin,

Li,

Chen

et al. 2024

J. Mater. Chem. B

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Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial

Cited by 60 publications

References 29 publications

Bacillus subtilismaintains antibiofilm activity againstStaphylococcus aureusfollowing adaptive laboratory evolution

Bacillus subtilismaintains antibiofilm activity againstStaphylococcus aureusfollowing adaptive laboratory evolution

Critical Assessment of the Prospects of Quorum-Quenching Therapy for Staphylococcus aureus Infection

Insights into the eradication of drug resistant Staphylococcus aureus via compound 6-nitrobenzo[cd]indole-2(1H)-ketone

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