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Gaudu, P.

Publications and source records attributed to Gaudu, P..

3 recordsLinked to original sources

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↗

Electrochemical biosensor based on NAD(P)H-dependent Quinone Reductase for rapid and efficient detection of vitamin K3

Vitamin K refers to a group of vitamins that play an important role in blood coagulation and regulation of bone and vascular metabolism. However, vitamin K3 may give severe side effects in animal and humans when improperly added to food and feed due to its toxicity. Here, an electrochemical biosensor, based on the YaiB NADPH-dependent quinone reductase from Lactococcus lactis (YaiB), was developed to achieve rapid and redox probe-free detection of vitamin K3. First, we demonstrated the ability of the carbon electrode to distinguish between 1,4-benzoquinone and hydroquinone. Then, we engineered YaiB to work as a bioreceptor immobilized at the electrode and we demonstrated its sensitivity and specificity to reduce vitamin K3. Finally, to demonstrate the practical potential of the biosensor, we tested it directly in spiked milk samples, achieving 15-minute quantification of the vitamin K3. The limit of detection was 0.18M and 0.86 M in buffer and milk, respectively.

biophysics↗

Staphylococcus aureus prophages are gatekeepers of exogenous lipid utilization to control membrane flexibility and bacterial fitness

Phages are ubiquitous in bacteria, including clinical Staphylococcus aureus, where Sfi 21/Sa3 phages often integrate into the hlb gene, encoding Hlb sphingomyelinase. The integration acts as a rapid regulatory switch of Hlb production. Our findings suggest that Sfi 21/Sa3 prophages and Hlb activity affect S. aureus fitness by modulating the incorporation of the toxic linoleic acid (C18:2) from serum into the bacterial membrane. This process relies on C18:2 derived from 1,3-diglyceride, facilitated by the FakB1 kinase subunit. Palmitic acid (C16), primarily released from serum through Hlb activity, competes for FakB1. This mechanism contributes to adaptation to AFN-1252, an antibiotic inhibiting the fatty acid synthesis pathway (anti-FASII). Since S. aureus relies on exogenous fatty acids for growth, AFN-1252 treatment leads to increased proportion of membrane C18:2. Moreover, Hlb inhibition, whether via prophage insertion, gene inactivation, or enzyme inhibition, delays S. aureus adaptation, resulting in higher proportionof C18:2 in the membrane. This study sheds light on the role of lipid environments in infections, and may contribute to the accurate prediction of infection risks and therapeutic efficacy. Furthermore, given that both anti-FASII and Hlb inhibitors enhance C18:2 incorporation, they represent potential agents for combined strategies against S. aureus.

microbiology↗