Biology subjects

Martinez-Lopez, N.

Publications and source records attributed to Martinez-Lopez, N..

3 recordsLinked to original sources

bioRxiv2026

A growth-survival trade-off quantitatively predicts microbial selection under periodic disinfection

AO_SCPLOWBSTRACTC_SCPLOWMicrobial populations frequently experience periodic lethal stresses from natural and anthropogenic sources, including routine disinfection in clinical, industrial, and domestic environments. However, periodic disinfection can rapidly select for tolerant strains with increased survival but reduced growth during permissive conditions, creating a trade-off that shapes competitive outcomes in microbial communities. Here, we develop a mathematical framework to quantify and predict selection between microbial strains competing for growth-limiting resources under periodic disinfection. The framework is validated through a competition experiment simulating periodic disinfection with benzalkonium chloride between a wild-type Escherichia coli strain and a tolerant mutant exhibiting increased survival but decreased growth. A minimal model incorporating growth rate during permissive conditions and disinfection survival quantitatively captures selection across different experimental scenarios, including uncertainty estimates propagated from parameter variance. We further provide analytical expressions and a web-based interface to determine selection outcomes and quantify the contributions of survival and growth rate to selection. Our framework establishes a quantitative basis for predicting when periodic disinfection shifts population composition towards tolerant strains and is generalizable to other lethal stresses, including antibiotic chemotherapy and physical inactivation, thereby contributing to our understanding of the impact of periodic selective pressures on microbial competition.

microbiology↗

bioRxiv2022

mTORC2 couples fasting to mitochondrial fission

Fasting triggers diverse cellular and metabolic adaptations to facilitate organismal survival1,2. During nutrient deprivation, increases in circulating fatty acids support mitochondrial respiration2. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during nutrient deprivation remain incompletely understood. Here we show that extended periods of fasting, or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its target NDRG13 at S336 sustains mitochondrial fission and respiratory sufficiency. Timelapse imaging reveals that wildtype NDRG1, but not phosphorylation-deficient NDRG1S336A mutant, engages with mitochondria to facilitate its scission. Using proteomics, and an siRNA screen, we show that mTORC2-phosphorylated NDRG1 cooperates with the small GTPase Cdc424 and Cdc42-specific effectors and regulators to orchestrate fission. Accordingly, RictorKO, NDRG1S336A mutants, and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions5; however, paradoxical reactivation of mTORC2 during fasting plays an unexpected role in driving mitochondrial fission and respiration.

cell biology↗

bioRxiv2020

Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1, CD204) expression is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a cohort of 170 NAFLD patients. Mice lacking Msr1 are protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation, improved dyslipidemia and glucose tolerance, while showing a change in hepatic lipid metabolism. We show that MSR1 induces a pro-inflammatory response via the JNK signaling pathway upon triggering by saturated fatty acids. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNFa. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and ex vivo human liver slices resulted in the prevention of foamy macrophage formation and liver inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate transaminase levels in a cohort of over 400,000 patients. Taken together, our data suggest a critical role for MSR1 in lipid homeostasis and a potential therapeutic target for the treatment of NAFLD. One Sentence SummaryThe immunometabolic role of MSR1 in human NAFLD.

immunology↗