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Microbiology and Environmental Toxicology

UC Santa Cruz

Open Access Policy Deposits

This series is automatically populated with publications deposited by UC Santa Cruz Department of Microbiology and Environmental Toxicology researchers in accordance with the University of California’s open access policies. For more information see Open Access Policy Deposits and the UC Publication Management System.

Cover page of Ordered assembly of the Vibrio cholerae biofilm exopolysaccharide defined by lipid-linked intermediate profiling.

Ordered assembly of the Vibrio cholerae biofilm exopolysaccharide defined by lipid-linked intermediate profiling.

(2026)

Biofilm formation underlies the environmental persistence and transmission of Vibrio cholerae, the etiological agent of cholera. The Vibrio polysaccharide (VPS) is the principal structural component of the mature biofilm matrix, yet the enzymatic logic governing its assembly has remained incompletely defined. VPS is synthesized as two closely related polymers that share a tetrasaccharide repeat unit but differ at a single monosaccharide position. Here, we systematically define VPS assembly by integrating targeted gene deletions with liquid chromatography-mass spectrometry profiling of lipid-linked intermediates, and comparative structural modeling of biosynthetic enzymes. Our results establish that VPS is produced through an ordered Wzx/Wzy-dependent pathway. VpsL functions as the initiating phosphoglycosyltransferase, generating bactoprenyl diphosphate-linked glucose. A VpsA/VpsB/VpsK module analogous to the enterobacterial common antigen machinery synthesizes and transfers an N-acetyl-mannosaminuronic acid (ManNAcA)-derived residue, after which VpsJ, which we propose as a new class of epimerase, catalyzes C5 epimerization to generate the rare bacterial sugar L-N-acetyl-gulosaminuronic acid (L-GulNAcA). Additional tailoring reactions mediated by VpsH, a previously unidentified protein with few sequence or structural homologs, and VpsG introduce glycine and acetyl modifications that are dispensable for repeat-unit assembly but influence matrix properties. Subsequently, glycosyltransfer reactions by VpsI and VpsD complete the tetrasaccharide repeat unit, with VpsD exhibiting substrate flexibility that accounts for the formation of both major and minor VPS variants. Downstream, VpsE and VpsF act following repeat-unit assembly, consistent with flippase and polymerase functions, respectively. Together, our findings establish a molecular framework for VPS assembly and deepen our understanding of the mechanisms that drive biofilm formation in Vibrio cholerae.IMPORTANCEBiofilm formation is an integral part of Vibrio cholerae's infection cycle, requiring production of the exopolysaccharide Vibrio polysaccharide (VPS). Together, these findings define the sequential enzymatic steps of VPS biosynthesis. This molecular map of VPS production identifies multiple enzymatic nodes as potential anti-biofilm targets and provides a mechanistic foundation for understanding how V. cholerae modulates biofilm architecture to enhance environmental survival and transmission.

Cover page of Regulation of the Yersinia pseudotuberculosis Type III Secretion System by the CpxAR Two‐Component System

Regulation of the Yersinia pseudotuberculosis Type III Secretion System by the CpxAR Two‐Component System

(2026)

The type III secretion system (T3SS) is a cell envelope-spanning injectisome found in many Gram-negative pathogens. Expression of the T3SS is controlled by extracellular signals such as cell envelope stress. The CpxAR two-component system negatively regulates the Yersinia pseudotuberculosis Ysc T3SS, although the mechanism remains unclear. As expected, we found that mutants with constitutive CpxR activity (∆cpxA and cpxRD51E) led to decreased expression of the Ysc T3SS and its master regulator LcrF. CpxR did not bind to the regulatory regions of lcrF, suggesting an indirect mechanism of regulation. Transcriptome analysis showed that 101 genes were upregulated and 77 genes downregulated in both the ∆cpxA and cpxRD51E strains compared to wildtype, including seven genes known to modulate transcription. Individual deletion of these seven regulatory factors did not identify any single gene responsible for CpxR-dependent repression of LcrF, suggesting that CpxAR may act through multiple pathways to regulate the Ysc T3SS. However, this analysis led us to examine the role of the osmolarity sensing two-component regulatory system OmpR/EnvZ. Deletion of ompR led to an increase in LcrF and T3SS expression. These results suggest more complex regulation of the Ysc T3SS by two-component regulatory systems than previously appreciated.

Cover page of Combined effective field theory interpretation of Higgs boson, electroweak vector boson, top quark, and multijet measurements

Combined effective field theory interpretation of Higgs boson, electroweak vector boson, top quark, and multijet measurements

(2026)

Constraints on Wilson coefficients (WCs) corresponding to dimension-6 operators of the standard model effective field theory (SMEFT) are determined from a simultaneous fit to seven sets of CMS measurements probing Higgs boson, electroweak vector boson, top quark, and multijet production. Measurements of electroweak precision observables are also included and provide complementary constraints to those from the CMS experiment. The CMS measurements, using LHC proton-proton collision data at s=13Te$$\sqrt{s}=13\,\text {Te}\text {V} $$, corresponding to integrated luminosities of 36.3 or 138fb-1$$\,\text {fb}^{-1}$$, are chosen to provide sensitivity to a broad set of operators, for which consistent SMEFT predictions can be derived. These are primarily measurements of differential cross sections which are parameterized as functions of the WCs. In measurements targeting t(t¯)X$${\text {t}} (\bar{\textrm{t}})\text {X} $$ production, SMEFT effects are modelled at the detector level. Individual constraints on 64 WCs, and constraints on 43 linear combinations of WCs, are obtained.

Cover page of Measurement of the Higgs boson mass and width using the four-lepton final state in proton-proton collisions at s=13 TeV

Measurement of the Higgs boson mass and width using the four-lepton final state in proton-proton collisions at s=13 TeV

(2025)

A measurement of the Higgs boson mass and width via its decay to two bosons is presented. Proton-proton collision data collected by the CMS experiment, corresponding to an integrated luminosity of at a center-of-mass energy of 13 TeV, is used. The invariant mass distribution of four leptons in the on-shell Higgs boson decay is used to measure its mass and constrain its width. This yields the most precise single measurement of the Higgs boson mass to date, , and an upper limit on the width at 95% confidence level. A combination of the on- and off-shell Higgs boson production decaying to four leptons is used to determine the Higgs boson width, assuming that no new virtual particles affect the production, a premise that is tested by adding new heavy particles in the gluon fusion loop model. This result is combined with a previous CMS analysis of the off-shell Higgs boson production with decay to two leptons and two neutrinos, giving a measured Higgs boson width of , in agreement with the standard model prediction of 4.1 MeV. The strength of the off-shell Higgs boson production is also reported. The scenario of no off-shell Higgs boson production is excluded at a confidence level corresponding to 3.8 standard deviations.

Cover page of Measurement of inclusive and differential cross sections for W+W− production in proton-proton collisions at s = 13.6 TeV

Measurement of inclusive and differential cross sections for W+W− production in proton-proton collisions at s = 13.6 TeV

(2025)

Measurements at s = 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb − 1 . Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavor and charge of the leptons, the number of jets, and number of jets originating from b quarks. The overall sensitivity is significantly better than that of previous results with a similar integrated luminosity. The improvement comes from a more refined control of experimental uncertainties and an improved fit strategy. An inclusive W + W − production cross section of 125.7 ± 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector acceptance, both inclusively and differentially, as a function of the jet multiplicity in the event. For the first time in proton-proton collisions, W W events with zero, one, and at least two jets are studied simultaneously and compared with recent theoretical predictions.

Cover page of Constraints on the Higgs boson self-coupling from the combination of single and double Higgs boson production in proton-proton collisions at s = 13 TeV

Constraints on the Higgs boson self-coupling from the combination of single and double Higgs boson production in proton-proton collisions at s = 13 TeV

(2025)

The Higgs boson (H) trilinear self-coupling, λ 3 , is constrained via its measured properties and limits on the HH pair production using the proton-proton collision data collected by the CMS experiment at s = 13 TeV . The combination of event categories enriched in single-H and HH events is used to measure κ λ , defined as the value of λ 3 normalized to its standard model prediction, while simultaneously constraining the Higgs boson couplings to fermions and vector bosons. Values of κ λ outside the interval − 1.2 < κ λ < 7.5 are excluded at 2σ confidence level, which is compatible with the expected range of − 2.0 < κ λ < 7.7 under the assumption that all other Higgs boson couplings are equal to their standard model predicted values. Relaxing the assumption on the Higgs couplings to fermions and vector bosons the observed (expected) κ λ interval is constrained to be within − 1.4 < κ λ < 7.8 ( − 2.3 < κ λ < 7.8 ) at 2σ confidence level.

Cover page of Girth and groomed radius of jets recoiling against isolated photons in lead-lead and proton-proton collisions at s NN = 5.02 &nbsp;TeV

Girth and groomed radius of jets recoiling against isolated photons in lead-lead and proton-proton collisions at s NN = 5.02  TeV

(2025)

This Letter presents the first measurements of the groomed jet radius R g and the jet girth g in events with an isolated photon recoiling against a jet in lead-lead (PbPb) and proton-proton (pp) collisions at the LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The observables R g and g provide a quantitative measure of how narrow or broad a jet is. The analysis uses PbPb and pp data samples with integrated luminosities of 1.7  nb − 1 and 301  pb − 1 , respectively, collected with the CMS experiment in 2018 and 2017. Events are required to have a photon with transverse momentum p T γ > 100  GeV and at least one jet back-to-back in azimuth with respect to the photon and with transverse momentum p T jet such that p T jet / p T γ > 0.4 . The measured R g and g distributions are unfolded to the particle level, which facilitates the comparison between the PbPb and pp results and with theoretical predictions. It is found that jets with p T jet / p T γ > 0.8 , i.e., those that closely balance the photon p T γ , are narrower in PbPb than in pp collisions. Relaxing the selection to include jets with p T jet / p T γ > 0.4 reduces the narrowing of the angular structure of jets in PbPb relative to the pp reference. This shows that selection bias effects associated with jet energy loss play an important role in the interpretation of jet substructure measurements.

Cover page of Helicobacter pylori luxS mutants cause hyperinflammatory responses during chronic infection

Helicobacter pylori luxS mutants cause hyperinflammatory responses during chronic infection

(2025)

Helicobacter pylori infects roughly half the world's population, causing gastritis, peptic ulcers, and gastric cancer in a subset. These pathologies occur in response to a chronic inflammatory state, but it is not fully understood how H. pylori controls this process. We characterized the inflammatory response of H. pylori mutants that cannot produce the quorum sensing molecule autoinducer 2 (AI-2) by deleting the gene for the AI-2 synthase, luxS. Our work shows that H. pylori luxS mutants colonize the stomach normally but recruit high numbers of CD4+ T cells to the stomach during chronic infection. This increase in the number of CD4+ T cells correlated with elevated expression of CXCL9, a chemokine important for T cell recruitment. Together, our results suggest that H. pylori may utilize AI-2 signaling to modulate the inflammatory response during chronic infection. IMPORTANCE: Many bacteria signal to each other using quorum sensing signals. One type of signal is called autoinducer 2 (AI-2), which is produced and sensed by the LuxS enzyme found in many bacteria, including the gastric pathogen Helicobacter pylori. H. pylori establishes chronic infections that last for decades and lead to serious disease outcomes. How AI-2 signaling and LuxS contribute to chronic H. pylori infection has not been studied. In this work, we analyzed how loss of H. pylori-created AI-2, via mutation of luxS, affects H. pylori chronic infection. luxS mutants did not have significant colonization defects, similar to their reported phenotype during early infection, but they did have high stomach levels of effector and regulatory T cells and T-cell-recruiting chemokines. These results suggest that H. pylori LuxS may play more of a role in modulating the immune response versus colonization.

Cover page of Search for bottom quark associated production of the standard model Higgs boson in final states with leptons in proton-proton collisions at s = 13 TeV

Search for bottom quark associated production of the standard model Higgs boson in final states with leptons in proton-proton collisions at s = 13 TeV

(2025)

This Letter presents the first search for bottom quark associated production of the standard model Higgs boson, in final states with leptons. Higgs boson decays to pairs of tau leptons and pairs of leptonically decaying W bosons are considered. The search is performed using data collected from 2016 to 2018 by the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb − 1 . Upper limits at the 95% confidence level are placed on the signal strength for Higgs boson production in association with bottom quarks; the observed (expected) upper limit is 3.7 (6.1) times the standard model prediction.

Cover page of Water, sanitation, handwashing, and nutritional interventions can reduce child antibiotic use: evidence from Bangladesh and Kenya

Water, sanitation, handwashing, and nutritional interventions can reduce child antibiotic use: evidence from Bangladesh and Kenya

(2025)

Antibiotics can trigger antimicrobial resistance and microbiome alterations. Reducing pathogen exposure and undernutrition can reduce infections and antibiotic use. We assess effects of water, sanitation, handwashing (WSH) and nutrition interventions on caregiver-reported antibiotic use in Bangladesh and Kenya, longitudinally measured at three timepoints among birth cohorts (ages 3–28 months) in a cluster-randomized trial. Over 50% of children used antibiotics at least once in the 90 days preceding data collection. In Bangladesh, the prevalence of antibiotic use was 10–14% lower in groups receiving WSH (prevalence ratio [PR] = 0.90 (0.82–0.99)), nutrition (PR = 0.86 (0.78–0.94)), and nutrition+WSH (PR = 0.86 (0.79–0.93)) interventions. The prevalence of using antibiotics multiple times was 26–35% lower in intervention arms. Reductions were largest when the birth cohort was younger. In Kenya, interventions did not affect antibiotic use. In this work, we show that improving WSH and nutrition can reduce antibiotic use. Studies should assess whether such reductions translate to reduced antimicrobial resistance.

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