Protein posttranslational modifications (PTMs), particularly phosphorylation, dramatically expand the complexity of cellular regulatory networks. Although cysteine (Cys) in various proteins can be subject to multiple PTMs, its phosphorylation was previously considered a rare PTM with almost no regulatory role assigned. We report here that phosphorylation occurs to a reactive cysteine residue conserved in the staphylococcal accessary regulator A (SarA)/MarR family global transcriptional regulator A (MgrA) family of proteins, and is mediated by the eukaryotic-like kinase-phosphatase pair Stk1-Stp1 in Staphylococcus aureus. Cys-phosphorylation is crucial in regulating virulence determinant production and bacterial resistance to vancomycin. Cell wall-targeting antibiotics, such as vancomycin and ceftriaxone, inhibit the kinase activity of Stk1 and lead to decreased Cys-phosphorylation of SarA and MgrA. An in vivo mouse model of infection established that the absence of stp1, which results in elevated protein Cys-phosphorylation, significantly reduces staphylococcal virulence. Our data indicate that Cys-phosphorylation is a unique PTM that can play crucial roles in bacterial signaling and regulation.

Oxidation sensing and quorum sensing significantly affect bacterial physiology and host-pathogen interactions. However, little attention has been paid to the cross-talk between these two seemingly orthogonal signaling pathways. Here we show that the quorum-sensing agr system has a built-in oxidation-sensing mechanism through an intramolecular disulfide switch possessed by the DNA-binding domain of the response regulator AgrA. Biochemical and mass spectrometric analysis revealed that oxidation induces the intracellular disulfide bond formation between Cys-199 and Cys-228, thus leading to dissociation of AgrA from DNA. Molecular dynamics (MD) simulations suggest that the disulfide bond formation generates a steric clash responsible for the abolished DNA binding of the oxidized AgrA. Mutagenesis studies further established that Cys-199 is crucial for oxidation sensing. The oxidation-sensing role of Cys-199 is further supported by the observation that the mutant Staphylococcus aureus strain expressing AgrAC199S is more susceptible to H 2 O 2 owing to repression of the antioxidant bsaA gene under oxidative stress. Together, our results show that oxidation sensing is a component of the quorum-sensing agr signaling system, which serves as an intrinsic checkpoint to ameliorate the oxidation burden caused by intense metabolic activity and potential host immune response.

Bed bugs have reemerged in the United States and worldwide over recent decades, presenting a major challenge to both public health practitioners and housing authorities. A number of municipalities have proposed or initiated policies to stem the bed bug epidemic, but little guidance is available to evaluate them. One contentious policy is disclosure, whereby landlords are obligated to notify potential tenants of current or prior bed bug infestations. Aimed to protect tenants from leasing an infested rental unit, disclosure also creates a kind of quarantine, partially and temporarily removing infested units from the market. Here, we develop a mathematical model for the spread of bed bugs in a generalized rental market, calibrate it to parameters of bed bug dispersion and housing turnover, and use it to evaluate the costs and benefits of disclosure policies to landlords. We find disclosure to be an effective control policy to curb infestation prevalence. Over the short term (within 5 years), disclosure policies result in modest increases in cost to landlords, while over the long term, reductions of infestation prevalence lead, on average, to savings. These results are insensitive to different assumptions regarding the prevalence of infestation, rate of introduction of bed bugs from other municipalities, and the strength of the quarantine effect created by disclosure. Beyond its application to bed bugs, our model offers a framework to evaluate policies to curtail the spread of household pests and is appropriate for systems in which spillover effects result in highly nonlinear cost–benefit relationships.

No abstract

Guinea pigs are important reservoirs of Trypanosoma cruzi, the causative parasite of Chagas disease. Interestingly, captured colonies of T. infestans, the main vector of T. cruzi in the Southern Cone of South America, sporadically present with infection prevalence rates above 80%. Such high values are not consistent with the relatively short 7–8 week parasitemic period that has been reported in the literature. We experimentally measured the infectious periods of a group of T. cruzi-infected guinea pigs with two methods: xenodiagnosis and direct microscopy, each performed weekly for a year. Another group of infected guinea pigs received only direct microscopy weekly, to control for the effect that inoculation by triatomine saliva may have on parasitemia in the host. We observed infectious periods longer than those previously reported in a number of guinea pigs from both the xenodiagnosis and control groups. While some guinea pigs were infectious for a short time, other “super-shedders” were parasitemic up to 22 weeks after infection, and/or positive by xenodiagnosis for a year after infection. This heterogeneity in infectiousness has strong implications for T. cruzi transmission dynamics and control, as super-shedder guinea pigs may play a disproportionate role in pathogen spread.