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Journal articleVincent CS, Beckwith E, Simoes da Silva C, et al., 2022,
Infection increases activity via Toll dependent and independent mechanisms in <i>Drosophila melanogaster</i>
, PLOS PATHOGENS, Vol: 18, ISSN: 1553-7366- Author Web Link
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- Citations: 1
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Journal articleWang G, Brunel J-M, Preusse M, et al., 2022,
The membrane-active polyaminoisoprenyl compound NV716 re-sensitizes <i>Pseudomonas aeruginosa</i> to antibiotics and reduces bacterial virulence
, COMMUNICATIONS BIOLOGY, Vol: 5- Author Web Link
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- Citations: 5
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Journal articlePizzato J, Tang W, Bernabeu S, et al., 2022,
Discrimination of Escherichia coli, Shigella flexneri, and Shigella sonnei using lipid profiling by MALDI-TOF mass spectrometry paired with machine learning
, MicrobiologyOpen, Vol: 11, Pages: 1-14, ISSN: 2045-8827Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has become a staple in clinical microbiology laboratories. Protein-profiling of bacteria using this technique has accelerated the identification of pathogens in diagnostic workflows. Recently, lipid profiling has emerged as a way to complement bacterial identification where protein-based methods fail to provide accurate results. This study aimed to address the challenge of rapid discrimination between Escherichia coli and Shigella spp. using MALDI-TOF MS in the negative ion mode for lipid profiling coupled with machine learning. Both E. coli and Shigella species are closely related; they share high sequence homology, reported for 16S rRNA gene sequence similarities between E. coli and Shigella spp. exceeding 99%, and a similar protein expression pattern but are epidemiologically distinct. A bacterial collection of 45 E. coli, 48 Shigella flexneri, and 62 Shigella sonnei clinical isolates were submitted to lipid profiling in negative ion mode using the MALDI Biotyper Sirius® system after treatment with mild-acid hydrolysis (acetic acid 1% v/v for 15 min at 98°C). Spectra were then analyzed using our in-house machine learning algorithm and top-ranked features used for the discrimination of the bacterial species. Here, as a proof-of-concept, we showed that lipid profiling might have the potential to differentiate E. coli from Shigella species using the analysis of the top five ranked features obtained by MALDI-TOF MS in the negative ion mode of the MALDI Biotyper Sirius® system. Based on this new approach, MALDI-TOF MS analysis of lipids might help pave the way toward these goals.
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Journal articleFillol-Salom A, Rostøl JT, Ojiogu AD, et al., 2022,
Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors
, Cell, Vol: 185, Pages: 3248-3262.e20, ISSN: 0092-8674Bacteria encode sophisticated anti-phage systems that are diverse and versatile and display high genetic mobility. How this variability and mobility occurs remains largely unknown. Here, we demonstrate that a widespread family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), carry an impressive arsenal of defense mechanisms, which can be disseminated intra- and inter-generically by helper phages. These defense systems provide broad immunity, blocking not only phage reproduction, but also plasmid and non-cognate PICI transfer. Our results demonstrate that phages can mobilize PICI-encoded immunity systems to use them against other mobile genetic elements, which compete with the phages for the same bacterial hosts. Therefore, despite the cost, mobilization of PICIs may be beneficial for phages, PICIs, and bacteria in nature. Our results suggest that PICIs are important players controlling horizontal gene transfer and that PICIs and phages establish mutualistic interactions that drive bacterial ecology and evolution.
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Journal articleFarne H, Lin L, Jackson D, et al., 2022,
In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection
, Thorax, Vol: 77, Pages: 929-932, ISSN: 0040-6376Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-β given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes four days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms. Our data indicate that the in vivo innate antiviral response is dysregulated in asthma and open up the potential that prophylactic rather than therapeutic interferon therapy may have greater clinical benefit.
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Journal articleWadhawan A, Simoes da Silva CJ, Nunes CD, et al., 2022,
<i>E. faecalis</i>acquires resistance to antimicrobials and insect immunity via common mechanisms
<jats:title>Summary</jats:title><jats:p><jats:italic>Enterococcus faecalis</jats:italic>is a normal member of the gut microbiota and an opportunistic pathogen of many animals, including mammals, birds, and insects. It is a common cause of nosocomial infections, and is particularly troublesome due to extensive intrinsic and acquired antimicrobial resistance. Using experimental evolution, we generated<jats:italic>Drosophila</jats:italic>-adapted<jats:italic>E. faecalis</jats:italic>strains, which exhibited immune resistance, resulting in increased<jats:italic>in vivo</jats:italic>growth and virulence. Resistance was characterised by mutations in bacterial pathways responsive to cell envelope stress.<jats:italic>Drosophila</jats:italic>-adapted strains exhibited changes in sensitivity to relevant antimicrobials, including daptomycin and vancomycin. Evolved daptomycin-resistant strains harboured mutations in the same signalling systems, with some strains showing increased virulence similar to<jats:italic>Drosophila</jats:italic>-adapted strains. Our results show that common mechanisms provide a route to resistance to both antimicrobials and host immunity in<jats:italic>E. faecalis</jats:italic>and demonstrate that the selection and emergence of antibiotic resistance<jats:italic>in vivo</jats:italic>does not require antibiotic exposure.</jats:p><jats:sec><jats:title>One sentence summary</jats:title><jats:p>Host interaction can promote antimicrobial resistance and antimicrobial treatment can promote virulence in<jats:italic>E. faecalis</jats:italic>.</jats:p></jats:sec>
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Journal articleHamilton C, Olona A, Leishman S, et al., 2022,
NLRP3 inflammasome priming and activation are regulated by a phosphatidylinositol-dependent mechanism
, ImmunoHorizons, Vol: 6, ISSN: 2573-7732Imbalance in lipid homeostasis is associated with discrepancies in immune signaling and is tightly linked to metabolic disorders. The diverse ways in which lipids impact immune signaling, however, remain ambiguous. The phospholipid phosphatidylinositol (PI), which is implicated in numerous immune disorders, is chiefly defined by its phosphorylation status. By contrast, the significance of the two fatty acid chains attached to the PI remains unknown. Here, by employing a mass-spectrometry-based assay, we demonstrate a role for PI acyl group chains in regulating both the priming and activation steps of the NLRP3 inflammasome in mouse macrophages. In response to NLRP3 stimuli, cells deficient in ABC transporter ABCB1, which effluxes lipid derivatives, revealed defective inflammasome activation. Mechanistically, Abcb1-deficiency shifted the total PI configuration exhibiting a reduced ratio of short-chain to long-chain PI acyl lipids. Consequently, Abcb1-deficiency initiated the rapid degradation of TIRAP, the TLR adaptor protein which binds PI (4,5)-bisphosphate, resulting in defective TLR-dependent signaling, and thus NLRP3 expression. Moreover, this accompanied increased NLRP3 phosphorylation at the Ser291 position and contributed to blunted inflammasome activation. Exogenously supplementing WT cells with linoleic acid, but not arachidonic acid, reconfigured PI acyl chains. Accordingly, linoleic acid supplementation increased TIRAP degradation, elevated NLRP3 phosphorylation, and abrogated inflammasome activation. Furthermore, NLRP3 Ser291 phosphorylation was dependent on prostaglandin E2-induced protein kinase A signaling as pharmacological inhibition of this pathway in linoleic acid-enriched cells dephosphorylated NLRP3. Altogether, our study reveals a novel metabolic-inflammatory circuit which contributes to calibrating immune responses.
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Journal articleLarrouy-Maumus G, Thomson M, Nunta K, et al., 2022,
Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials
, Journal of Biological Chemistry, Vol: 298, ISSN: 0021-9258Antimicrobial tolerance, the ability to survive exposure to antimicrobials via transient nonspecific means, promotes the development of antimicrobial resistance (AMR). The study of the molecular mechanisms that result in antimicrobial tolerance is therefore essential for the understanding of AMR. In gram-negative bacteria, the second messenger molecule 3’,5’-cyclic adenosine monophosphate (cAMP) has been previously shown to be involved in AMR. In mycobacteria, however, the role of cAMP in antimicrobial tolerance has been difficult to probe due to its particular complexity. In order to address this difficulty, here, through an unbiased biochemical approaches consisting in the fractionation of clear protein lysate from a mycobacterial strain deleted for the known cAMP phosphodiesterase (Rv0805c) combined with mass spectrometry techniques, we identified a novel cyclic nucleotide-degrading phosphodiesterase enzyme (Rv1339) and developed a system to significantly decrease intracellular cAMP levels through plasmid expression of Rv1339 using the constitutive expression system, pVV16. In Mycobacterium smegmatis mc2155, we demonstrate that recombinant expression of Rv1339 reduced cAMP levels 3-fold and resulted in altered gene expression, impaired bioenergetics and a disruption in peptidoglycan biosynthesis leading to decreased tolerance to antimicrobials that target cell wall synthesis such as ethambutol, D-cycloserine and vancomycin. This work increases our understanding of the role of cAMP in mycobacterial antimicrobial tolerance and our observations suggest that nucleotide signaling may represent a new target for the development of antimicrobial therapies.
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Journal articleSingh S, Wilksch JJ, Dunstan RA, et al., 2022,
LPS O Antigen Plays a Key Role in Klebsiella pneumoniae Capsule Retention
, MICROBIOLOGY SPECTRUM, Vol: 10, ISSN: 2165-0497- Author Web Link
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- Citations: 7
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Journal articleChaukimath P, Frankel G, Visweswariah SS, 2023,
The metabolic impact of bacterial infection in the gut
, FEBS JOURNAL, ISSN: 1742-464X- Author Web Link
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- Citations: 1
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