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Pechoux, C.

Publications and source records attributed to Pechoux, C..

5 recordsLinked to original sources

The fatty acid synthesis pathway is a checkpoint for lipoteichoic acid synthesis in Staphylococcus aureus

Bacterial membranes comprise diverse lipids whose proportions vary according to environmental conditions. How cells direct lipid flux toward specific products remains unclear. We address this question in the human pathogen Staphylococcus aureus, where multiple lipid products compete for a common precursor, the major phospholipid, phosphatidylglycerol (PG). One product, lipoteichoic acid (LTA), is essential for cell division, envelope homeostasis, and virulence. Lipids and metabolites were quantified to identify factors that prioritize LTA synthesis over the other PG-derived products. We identify upstream fatty acid synthesis (FASII) pathway as a key control point for LTA production. Inhibition of FASII by antibiotics or gene inactivation causes LTA depletion. FASII inhibition similarly affects LTA in Streptococcus agalactiae, suggesting conservation of this LTA control strategy. Changes in membrane fatty acids do not account for LTA depletion. Instead, we show that FASII inhibition causes a drop in intracellular glycerophosphate (GroP), a precursor for both PG and LTA. Under these conditions of GroP limitation, PG flux favors production of a non-GroP lipid, cardiolipin. Moreover, combined inhibition of FASII and WTA blocks S. aureus growth, confirming the lethality of depleting LTA and WTA simultaneously. This study resolves how S. aureus manages phospholipid flux, by prioritizing the synthesis of GroP-rich LTA or of non-GroP-containing lipids according to FASII-controlled GroP availability.

microbiology↗

Versatility of Campylobacter jejuni Bf extracellular vesicles in regulating adaptation and virulence under combined thermal and oxidative stress

The high prevalence of aerotolerant human Campylobacter jejuni isolates suggests a correlation between the ability to survive in aerobic conditions, virulence and resistance to harsh stress conditions. However, the mechanisms are still unclear. Here, we investigated the role of bacterial extracellular vesicles (bEVs) in the adaptation of the clinical aerotolerant C. jejuni Bf strain to thermal and oxidative stress. We show that C. jejuni Bf survives and actively multiplies under this combined stress. Stress exposure induced cell rounding and loss of motility, remodeling of membrane composition, decreased membrane fluidity, and metabolic reprogramming with increased intracellular ATP levels. Lipidomic analyses further revealed that bEVs composition is markedly different from that of the parent membranes indicating that vesicle formation is selective and regulated. Although bEVs were produced in similar amounts under both microaerophilic and stress conditions, stress exposure generated significantly larger vesicles with greater diameter and dry mass, and altered their protein and lipid profiles. bEVs derived from stressed cells showed increased toxicity toward the epithelial barrier of Caco-2 cells. Taken together, these results indicate that C. jejuni bEV secretion is part of a survival strategy that connects environmental adaptation with pathogenicity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/714464v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@17aa2aforg.highwire.dtl.DTLVardef@4eab9dorg.highwire.dtl.DTLVardef@e4fba8org.highwire.dtl.DTLVardef@146109a_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Biotope-dependent High Level Resistance to Reactive Oxygen Species, Antibiotic Tolerance, and Virulence of Staphylococcus aureus

The human and livestock pathogen Staphylococcus aureus poses a major clinical challenge due to antibiotic treatment failure. Its resilience is mainly attributed to antibiotic resistance and tolerance mechanisms related to persistence. Here we investigate how two infection-relevant biotopes, milk and serum, shape S. aureus pathogenic properties and capacity to withstand environmental stresses. Milk-versus serum-adapted bacteria show gross differences in envelope physical properties, membrane fatty acid composition and rigidity, and pigment production, and display distinct proteomic profiles. Compared to serum, milk adaptation of S. aureus confers extreme resistance to ROS damage, pronounced antimicrobial tolerance, and accelerated killing in an insect infection model. High level S. aureus pigmentation in whole milk is stimulated by milk lipids, and is responsible for high ROS resistance. The remarkable robustness of S. aureus in a milk biotope may signal the need to adjust antibiotic regimens when treating mastitis infections in humans and livestock.

microbiology↗

Complex sporulation-specific expression of transcription termination factor Rho highlights its involvement in Bacillus subtilis cell differentiation

Transcription termination factor Rho controls pervasive, mainly antisense, transcription initiated at cryptic signals or resulting from read-through at weak terminators in various bacterial species. In Bacillus subtilis, Rho is intricately involved in the regulation of phenomena associated with the adaptation to stationary phase and cell differentiation including the ultimate survival program of sporulation. While knockout or overexpression of the rho gene alters global transcription and modifies cell physiology, in wild-type B. subtilis cells, the reduction of Rho levels during the transition to stationary phase is necessary for both initiation and implementation of the sporulation program. However, the mechanisms that govern Rho expression throughout the cell cycle remain largely unknown. Here, we demonstrate that, besides the previously identified vegetative SigA-dependent promoter active during exponential growth, two distinct mechanisms ensure a spatiotemporal expression of the rho gene during sporulation. In the mother cell of the sporangium, rho expression occurs through the read-through transcription initiated at the distal SigH-dependent and Spo0A[~]P-regulated promoter of the spo0F gene. In the forespore, rho is transcribed from a genuine promoter recognized by the alternative sigma factor SigF. These regulatory elements compensate for the inactivation of SigA-dependent rho expression at the end of exponential growth and allow the critical "refueling" of Rho protein in both compartments of the sporangium. We show that altering rho expression in the mother cell or in the forespore affects differently the properties and the morphology of mature spores. Moreover, spores formed in the absence of Rho are impaired in their ability to revive under favorable growth conditions, exhibiting accelerated germination and slow outgrowth. Finally, we show that optimal outgrowth of the wild-type spores requires the expression of rho during spore maturation and additionally after spore germination.

microbiology↗

Massive detection of cryptic recessive genetic defects in cattle mining millions of life histories

We present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

genetics↗