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Streptococcus mutans is the primary etiological agent of human dental caries and, at times, of infective endocarditis. Within the oral cavity, the pathogen is subjected to conditions of stress. A well-conserved protein complex named ClpP (caseinolytic protease) plays a vital role in adaptation under stress conditions. To gain a better understanding of the global role of the ClpP protease in cellular homeostasis, a transcriptome analysis was performed using a [DELTA]clpP mutant strain. The expression levels of more than 100 genes were up- or downregulated in the [DELTA]clpP mutant compared to the wild type. Notably, the expression of genes in several genomic islands, such as TnSmul and TnSmu2, was differentially modulated in the [DELTA]clpP mutant strain. ClpP deficiency also increased the expression of genes associated with a putative CRISPR locus. Furthermore, several stress-related genes and genes encoding bacteriocin-related peptides and many transcription factors were also found to be altered in the [DELTA]clpP mutant strain. A comparative analysis of the two-dimensional protein profile of the wild type and the [DELTA]clpP mutant strains showed altered protein profiles. Comparison of the transcriptome data with the proteomic data identified four common gene products, suggesting that the observed altered protein expression of these genes could be due to altered transcription. The results presented here indicate that ClpP-mediated proteolysis plays an important global role in the regulation of several important traits in this pathogen. doi: 10.1128/JB.01350-09

The gram-positive bacterium Streptococcus mutans is the primary causative agent in the formation of dental caries in humans. The ability ofS. mutans to adapt and to thrive in the hostile environment of the oral cavity suggests that this cariogenic pathogen is capable of sensing and responding to different environmental stimuli. This prompted us to investigate the role of two-component signal transduction systems (TCS), particularly the sensor kinases, in response to environmental stresses. Analysis of the annotated genome sequence ofS. mutans indicates the presence of 13 putative TCS. Further bioinformatics analysis in our laboratory has identified an additional TCS in the genome of S. mutans. We verified the presence of the 14 sensor kinases by using PCR and Southern hybridization in 13 different S. mutans strains and found that not all of the sensor kinases are encoded by each strain. To determine the potential role of each TCS in the stress tolerance ofS. mutans UAI59, insertion mutations were introduced into the genes encoding the individual sensor kinases. We were successful in inactivating all of the sensor kinases, indicating that none of the TCS are essential for the viability of S. mutans. The mutant S. mutans strains were assessed for their ability to withstand various stresses, including osmotic, thermal, oxidative, and antibiotic stress, as well as the capacity to produce mutacin. We identified three sensor kinases, Smu486, Smul128, and Smul516, which play significant roles in stress tolerance of S. mutans strain UA159.

Streptococcus mutans, the principal causative agent of dental caries, produces four glucan-binding proteins (Gbp) that play major roles in bacterial adherence and pathogenesis. One of these proteins, GbpC, is an important cell surface protein involved in biofilm formation. GbpC is also important for cariogenesis, bacteremia, and infective endocarditis. In this study, we examined the regulation of gbpC expression in S. mutans strain UA159. We found thatgbpC expression attains the maximum level at mid-exponential growth phase, and the half-life of the transcript is less than 2 min. Expression from PgbpC was measured using a PgbpC-gusA transcriptional fusion reporter and was analyzed under various stress conditions, including thermal, osmotic, and acid stresses. Expression of gbpC is induced under conditions of thermal stress but is repressed during growth at low pH, whereas osmotic stress had no effect on expression from PgbpC. The results from the expression analyses were further confirmed using semiquantitative reverse transcription-PCR analysis. Our results also reveal that CovR, a global response regulator in many Streptococcus spp., represses gbpC expression at the transcriptional level. We demonstrated that purified CovR protein binds directly to the promoter region of PgbpC to repress gbpC expression. Using a DNase I protection assay, we showed that CovR binds to DNA sequences surrounding PgbpC from bases -68 to 28 (where base 1 is the start of transcription). In summary, our results indicate that various stress conditions modulate the expression of gbpC and that CovR negatively regulates the expression of the gbpC gene by directly binding to the promoter region.

Streptococcus mutans is an important etiological agent of dental caries in humans. The extracellular polysaccharides synthesized by cell-associated glucosyltransferases (encoded by gtfBC) from sucrose have been recognized as one of the important virulence factors that promote cell aggregation and adherence to teeth, leading to dental plaque formation. In this study, we have characterized the effect of CovR, a global response regulator, on glucosyltransferase expression. Inactivation of covR in strain UA159 resulted in a marked increase in the GtfB and GtfC proteins, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With the use of a transcriptional reporter system of a single chromosomal copy of the PgtfB-gusA and PgtfC-gusA fusions, we confirmed the transcriptional regulation of these promoters by CovR. By in vitro electrophoretic mobility shift assays with purified CovR protein, we showed that CovR regulates these promoters directly. DNase I footprinting analyses suggest that CovR binds to large regions on these promoters near the transcription start sites. Taken together, our results indicate that CovR negatively regulates the expression of the gtfB and gtfC genes by directly binding to the promoter region.

Intricate functional diversities in marine ecosystems often lead to exhibit a variety of dynamical behaviors, including chaos. To bring order into such chaotic situations, the system develops different mechanisms of self‐adaptability. Our present investigation is based on the study of an eco‐epidemiological model for virally infected toxic phytoplankton and zooplankton system. Both healthy and infected phytoplankton are assumed to be exposed to grazer zooplankton with a varying degree of exposure. An extension is made by introducing the fact that viral replication process in a lysis event is mediated by some time lag. To achieve more realistic and explicit outcomes of the existing phenomena correlated with our model, we consider the force of infection and replication of free viruses as seasonally forced. We find that time delay accounts for recurrent stability switching event in the system. The chaotic behavior is observed in the seasonally forced delayed system, which indicates the emergence of harmful blooms. The main motive is to gain a clear insight into the field of synchronization and stabilization of the irregular behaviors of the system. Our investigations suggest that increased strength of toxic compounds exuded by phytoplankton species may suppress the prevalence of chaotic disorder and drives the system into a zooplankton‐free zone. The intensity of selective grazing of zooplankton changes the state of chaos to order and promotes the disease‐free system. [ABSTRACT FROM AUTHOR]

The 20011 Census of India has shown that there has been a perceptible decline in the child sex ratio and this has been going on at a relatively faster pace since the last few decades. The skewed child sex ratio, it is feared, will be of serious concern for the future age and sex composition of India's population as the masculinisation of society will create social problems as is happening in many of the states with very low sex ratio. This paper is of the view that the declining CSR is only a dimension of the undermining of the position of women in Indian society despite some women making it to the top. It is only a variant of the different measures in use to eliminate women and only the exercise of informed agency on the part of society and political will on the part of the state can bring in the changes necessary to check the decline and prevent the negative consequences of a gender deficit society. [ABSTRACT FROM AUTHOR]

Dental caries induced by Streptococcus mutans is one of the most prevalent chronic infectious diseases worldwide. The pathoge-nicity of S. mutans relies on the bacterium's ability to colonize tooth surfaces and survive a strongly acidic environment. We performed an I SS1 transposon mutagenesis to screen for acid-sensitive mutants of S. mutans and identified an SMU.746-SMU.747 gene cluster that is needed for aciduricity. SMU.746 and SMU.747 appear to be organized in an operon and encode a putative membrane-associated permease. SMU.746- and SMU.747-deficient mutants showed a reduced ability to grow in acidified medium. However, the short-term or long-term acid survival capacity and F1F0 ATPase activity remained unaffected in the mutants. Furthermore, deletion of both genes did not change cell membrane permeability and the oxidative and heat stress responses. Growth was severely affected even with slight acidification of the defined medium (pH 6.5). The ability of the mutant strain to acidify the defined medium during growth in the presence of glucose and sucrose was significantly reduced, although the glycolysis rate was only slightly affected. Surprisingly, deletion of the SMU.746-SMU.747 genes triggered increased biofilm formation in low-pH medium. The observed effects were more striking in a chemically defined medium. We speculate that the SMU.746-SMU.747 complex is responsible for amino acid transport, and we discuss its possible role in colonization and survival in the oral environment. [ABSTRACT FROM AUTHOR]

The tribes of India have been the focus of development initiatives ever since India achieved independence. In this paper an attempt has been made to study the condition of a section of the tribal tea garden workers of North Bengal. The workers under study are based in the tea plantations which have remained closed for a considerable period of time and have currently opened. They are going through a phase of periodic closure and opening. The condition of the workers has been sought to be studied in the context of tribal development initiatives and to find out whether these have any relevance for the workers in these gardens. [ABSTRACT FROM AUTHOR]

Streptococcus mutans, a principal causative agent of dental caries, is considered to be the most cariogenic among all oral streptococci. Of the four S. mutans serotypes (c, e, f, and k), serotype c strains predominate in the oral cavity. Here, we present the complete genome sequence of S. mutans GS-5, a serotype c strain originally isolated from human carious lesions, which is extensively used as a laboratory strain worldwide. [ABSTRACT FROM AUTHOR]

Importance: Cytoplasmic Clp-related proteases play a major role in maintaining cellular proteome in bacteria. ClpX/P is one such proteolytic complex that is important for conserving protein homeostasis. In this study, we investigated the role of ClpX/P in Streptococcus mutans , an important oral pathogen. We identified several putative substrates whose cellular levels are regulated by ClpX/P in S. mutans and subsequently discovered several recognition motifs that are critical for degradation. Our study is the first comprehensive analysis of determining ClpX/P motifs in streptococci. We believe that identifying the substrates that are regulated by ClpX/P will enhance our understanding about virulence regulation in this important group of pathogens., Competing Interests: The authors declare no conflict of interest.

Every successful species invasion is facilitated by both ecological and evolutionary mechanisms. The evolution of population's fitness related traits acts as functional adaptations to Allee effects. This trade-off increases predatory success at an expense of elevated death rate of potential predators. We address our queries employing an eco-evolutionary modeling approach that provides a means of circumventing inverse density-dependent effect. In the absence of evolution, the ecological system potentially exhibits multi-stable configurations under identical ecological conditions by allowing different bifurcation scenarios with the Allee effect. The model predicts a high risk of catastrophic extinction of interacting populations around different types of saddle-node bifurcations resulting from the increased Allee effect. We adopt the game-theoretic approach to derive the analytical conditions for the emergence of evolutionarily stable strategy (ESS) when the ecological system possesses asymptotically stable steady states as well as population cycles. We establish that ESSs occur at those values of adopted evolutionary strategies that are local optima of some functional forms of model parameters. Overall, our theoretical study provides important ecological insights in predicting successful biological invasions in the light of evolution., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

In this article, we contemplate the dynamics of a three-tier system of nutrient, phytoplankton, and zooplankton with a gestation delay of discrete type and a distributed delay in nutrient recycling. Phytoplankton secretion-mediated alteration in the grazing pattern of zooplankton is encapsulated by a Monod-Haldane functional response. We carry out global sensitivity analysis for identifying the crucial model parameters having a significant impact on zooplankton density. The system potentially exhibits bistable configurations under identical ecological conditions by allowing different bifurcation scenarios, including multiple saddle-node and transcritical bifurcations with varying input rates of nutrients and inhibitory effects of phytoplankton against zooplankton. We observe that the gestation delay in zooplankton is responsible for the emergence of noxious bloom events. Interestingly, when the delay parameter crosses a threshold, the system experiences chaotic disorder, which prognosticates the onset of irregular bloom. Furthermore, by adding Gaussian white noise, we have extended the deterministic model to its stochastic counterpart. We found that white noise appears to regulate the survival and extinction of interacting populations. Comprehensive numerical simulations are consistent with mathematical results prognosticated by linear analysis.

In the present study, we investigate the selective feeding of zooplankton on phytoplankton infected by free-viruses in the presence of environmental toxins in the marine ecosystem. The environmental toxins assume to decrease the growth rate of susceptible phytoplankton, and increase the death rate of infected phytoplankton and zooplankton. Global sensitivity analysis identifies important parameters of the system having crucial impact on the aquatic health. The coexistence equilibrium of the system stabilizes on increasing the parameters related to inhibition of phytoplankton growth due to environmental toxins and the force of infection, and destabilizes on increasing the carrying capacity of susceptible phytoplankton and preference of zooplankton on infected phytoplankton. The chance of extinction of free-viruses increases on increasing the preference of zooplankton on infected phytoplankton or decreasing the force of infection. Moreover, if the input rate of environmental toxins is high, then the system becomes zooplankton-free for higher values of force of infection. On increasing the values of preference of zooplankton on infected phytoplankton, the system exhibits transition from stable coexistence to oscillations around coexistence equilibrium to oscillations around disease-free equilibrium. We observe that the presence of free-viruses and environmental toxins in the system drive zooplankton population to very low equilibrium values but the ecological balance of the aquatic food web can be maintained by modulating the decay (depletion) rate of free-viruses (environmental toxins).

Unlabelled: Streptococcus mutans, a causative agent of dental caries, relies on multiple quorum-sensing (QS) pathways that coordinate the expression of factors needed for colonization in the oral cavity. S. mutans uses small peptides as QS signaling molecules that typically are secreted into the outside milieu. Competence-stimulating peptide (CSP) is one such QS signaling molecule that functions through the ComDE two-component signal transduction pathway. CSP is secreted through NlmTE, a dedicated ABC transporter that cleaves off the N-terminal leader peptide to generate a mature peptide that is 21 residues long (CSP-21). We recently identified a surface-localized protease, SepM, which further cleaves the CSP-21 peptide at the C-terminal end and removes the last 3 residues to generate CSP-18. CSP-18 is the active QS molecule that interacts with the ComD sensor kinase to activate the QS pathway. In this study, we show that SepM specifically cleaves CSP-21 between the Ala18 and Leu19 residues. We also show that SepM recognizes only Ala at position 18 and Leu at position 19, although some CSP-18 variants with a substitution at position 18 can function equally as well as the QS peptide. Furthermore, we demonstrate that SepM homologs from other streptococci are capable of processing CSP-21 to generate functional CSP-18., Importance: SepM is a membrane-associated streptococcal protease that processes competence-stimulating peptide (CSP) to generate an active quorum-sensing molecule in S. mutans. SepM belongs to the S16 family of serine proteases, and in this study, we found that SepM behaves as an endopeptidase. SepM displays strict substrate specificity and cleaves the peptide bond between the Ala and Leu residues. This is the first report of an endopeptidase that specifically cleaves these two residues., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)