scholarly journals Manganese uptake, mediated by SloABC and MntH, is essential for the fitness of Streptococcus mutans

2019 ◽  
Author(s):  
Jessica K. Kajfasz ◽  
Callahan Katrak ◽  
Tridib Ganguly ◽  
Jonathan Vargas ◽  
Logan Wright ◽  
...  

ABSTRACTEarly epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen Streptococcus mutans. To better understand the importance of manganese homeostasis to S. mutans pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of S. mutans UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were the entire sloABC operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, herein mntH, that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of sloC, which encodes the lipoprotein receptor of the SloABC system, or mntH alone had no major consequence on the overall fitness of S. mutans, simultaneous inactivation of sloC and mntH (ΔsloCΔmntH) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin. Further, disruption of Mn transport resulted in diminished stress tolerance and reduced biofilm formation in the presence of sucrose. These phenotypes were markedly improved when cells were provided with excess Mn. Metal quantifications revealed that the single mutant strains contain similar intracellular levels of Mn as the parent strain, whereas Mn was nearly undetectable in the ΔsloCΔmntH strain. Collectively, these results reveal that SloABC and MntH work independently and cooperatively to promote cell growth under Mn-restricted conditions, and that mauitanence of Mn homeostasis is essential for the expression of major virulence attributes in S. mutans.IMPORTANCEAs trace biometals such as manganese (Mn) are important for all forms of life, the ability to regulate biometals availability during infection is an essential trait of successful bacterial pathogens. Here, we showed that the caries pathogen Streptococcus mutans utilizes two Mn transport systems, namely SloABC and MntH, to acquire Mn from the environment, and that the ability to maintain the cellular levels of Mn is important for the manifestation of characteristics that associate S. mutans with dental caries. Our results indicate that the development of strategies to deprive S. mutans of Mn hold promise in the combat against this important bacterial pathogen.

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Jessica K. Kajfasz ◽  
Callahan Katrak ◽  
Tridib Ganguly ◽  
Jonathan Vargas ◽  
Logan Wright ◽  
...  

ABSTRACT Early epidemiological studies implicated manganese (Mn) as a possible caries-promoting agent, while laboratory studies have indicated that manganese stimulates the expression of virulence-related factors in the dental pathogen Streptococcus mutans. To better understand the importance of manganese homeostasis to S. mutans pathophysiology, we first used RNA sequencing to obtain the global transcriptional profile of S. mutans UA159 grown under Mn-restricted conditions. Among the most highly expressed genes were those of the entire sloABC operon, encoding a dual iron/manganese transporter, and an uncharacterized gene, here mntH, that codes for a protein bearing strong similarity to Nramp-type transporters. While inactivation of sloC, which encodes the lipoprotein receptor of the SloABC system, or of mntH alone had no major consequence for the overall fitness of S. mutans, simultaneous inactivation of sloC and mntH (ΔsloC ΔmntH) impaired growth and survival under Mn-restricted conditions, including in human saliva or in the presence of calprotectin. Further, disruption of Mn transport resulted in diminished stress tolerance and reduced biofilm formation in the presence of sucrose. These phenotypes were markedly improved when cells were provided with excess Mn. Metal quantifications revealed that the single mutant strains contained intracellular levels of Mn similar to those seen with the parent strain, whereas Mn was nearly undetectable in the ΔsloC ΔmntH strain. Collectively, these results reveal that SloABC and MntH work independently and cooperatively to promote cell growth under Mn-restricted conditions and that maintenance of Mn homeostasis is essential for the expression of major virulence attributes in S. mutans. IMPORTANCE As transition biometals such as manganese (Mn) are essential for all forms of life, the ability to scavenge biometals in the metal-restricted host environment is an important trait of successful cariogenic pathobionts. Here, we showed that the caries pathogen Streptococcus mutans utilizes two Mn transport systems, namely, SloABC and MntH, to acquire Mn from the environment and that the ability to maintain the cellular levels of Mn is important for the manifestation of characteristics that associate S. mutans with dental caries. Our results indicate that the development of strategies to deprive S. mutans of Mn hold promise in the combat against this important bacterial pathogen.


2016 ◽  
Vol 198 (7) ◽  
pp. 1087-1100 ◽  
Author(s):  
Gursonika Binepal ◽  
Kamal Gill ◽  
Paula Crowley ◽  
Martha Cordova ◽  
L. Jeannine Brady ◽  
...  

ABSTRACTPotassium (K+) is the most abundant cation in the fluids of dental biofilm. The biochemical and biophysical functions of K+and a variety of K+transport systems have been studied for most pathogenic bacteria but not for oral pathogens. In this study, we establish the modes of K+acquisition inStreptococcus mutansand the importance of K+homeostasis for its virulence attributes. TheS. mutansgenome harbors four putative K+transport systems that included two Trk-like transporters (designated Trk1 and Trk2), one glutamate/K+cotransporter (GlnQHMP), and a channel-like K+transport system (Kch). Mutants lacking Trk2 had significantly impaired growth, acidogenicity, aciduricity, and biofilm formation. [K+] less than 5 mM eliminated biofilm formation inS. mutans. The functionality of the Trk2 system was confirmed by complementing anEscherichia coliTK2420 mutant strain, which resulted in significant K+accumulation, improved growth, and survival under stress. Taken together, these results suggest that Trk2 is the main facet of the K+-dependent cellular response ofS. mutansto environment stresses.IMPORTANCEBiofilm formation and stress tolerance are important virulence properties of caries-causingStreptococcus mutans. To limit these properties of this bacterium, it is imperative to understand its survival mechanisms. Potassium is the most abundant cation in dental plaque, the natural environment ofS. mutans. K+is known to function in stress tolerance, and bacteria have specialized mechanisms for its uptake. However, there are no reports to identify or characterize specific K+transporters inS. mutans. We identified the most important system for K+homeostasis and its role in the biofilm formation, stress tolerance, and growth. We also show the requirement of environmental K+for the activity of biofilm-forming enzymes, which explains why such high levels of K+would favor biofilm formation.


Author(s):  
Young-Mee Kim ◽  
Sung-il Cho

Prior studies have found that exercise has a positive effect on depressive symptoms in the general population. For older individuals, however, the association between exercise and depressive symptoms is conclusive. We examined whether regular exercise is related to depressive symptoms in 5379 Korean adults aged ≥55 years using data from a 2016 survey administered in the Korean Longitudinal Study of Aging. We used the 10-item Center for Epidemiological Studies–Depression scale to assess depressive symptoms. We performed a multivariate logistic regression analysis to investigate the relationship between regular exercise and depressive symptoms, adjusting for sociodemographic characteristics, self-rated health, number of chronic diseases, body mass index, hand-grip strength, physical disability, cognitive impairment, and health behavior. Interaction terms, including regular exercise and health-related factors, were also added. We found that a lack of regular exercise was significantly related to an increased frequency of depressive symptoms (OR = 1.18, 95% CI = 1.03–1.35). Moreover, hand-grip strength may increase the effect of regular exercise on depressive symptoms in individuals 65 years and older (OR = 1.01 vs. 1.70, 95% CI = 1.05–1.96). Our results suggest that it is important to encourage older individuals to exercise regularly as a means of relieving depressive symptoms.


Author(s):  
Christine Lion ◽  
A. Lozniewski ◽  
M. Weissenbach ◽  
M. Weber

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Hiu Ham Lee ◽  
Preethi Sudhakara ◽  
Shreena Desai ◽  
Kildare Miranda ◽  
Luis R. Martinez

ABSTRACT “METH mouth” is a common consequence of chronic methamphetamine (METH) use, resulting in tooth decay and painful oral tissue inflammation that can progress to complete tooth loss. METH reduces the amount of saliva in the mouth, promoting bacterial growth, tooth decay, and oral tissue damage. This oral condition is worsened by METH users’ compulsive behavior, including high rates of consumption of sugary drinks, recurrent tooth grinding, and a lack of frequent oral hygiene. Streptococcus mutans is a Gram-positive bacterium found in the oral cavity and associated with caries in humans. Hence, we developed a murine model of METH administration, sugar intake, and S. mutans infection to mimic METH mouth in humans and to investigate the impact of this drug on tooth colonization. We demonstrated that the combination of METH and sucrose stimulates S. mutans tooth adhesion, growth, and biofilm formation in vivo. METH and sucrose increased the expression of S. mutans glycosyltransferases and lactic acid production. Moreover, METH contributes to the low environmental pH and S. mutans sucrose metabolism, providing a plausible mechanism for bacterium-mediated tooth decay. Daily oral rinse treatment with chlorhexidine significantly reduces tooth colonization in METH- and sucrose-treated mice. Furthermore, human saliva inhibits S. mutans colonization and biofilm formation after exposure to either sucrose or the combination of METH and sucrose. These findings suggest that METH might increase the risk of microbial dental disease in users, information that may help in the development of effective public health strategies to deal with this scourge in our society. IMPORTANCE “METH mouth” is characterized by severe tooth decay and gum disease, which often causes teeth to break or fall out. METH users are also prone to colonization by cariogenic bacteria such as Streptococcus mutans. In addition, this oral condition is aggravated by METH users’ compulsive behavior, including the consumption of beverages with high sugar content, recurrent tooth grinding, and a lack of frequent oral hygiene. We investigated the effects of METH and sugar consumption on S. mutans biofilm formation and tooth colonization. Using a murine model of METH administration, sucrose ingestion, and oral infection, we found that the combination of METH and sucrose increases S. mutans adhesion and biofilm formation on the teeth of C57BL/6 mice. However, daily chlorhexidine-based oral rinse treatment reduces S. mutans tooth colonization. Similarly, METH has been associated with dry mouth or hyposalivation in users. Hence, we assessed the impact of human saliva on biofilm formation and demonstrated that surface preconditioning with saliva substantially reduces S. mutans biofilm formation. Our results are significant because to our knowledge, this is the first basic science study focused on elucidating the fundamentals of METH mouth using a rodent model of prolonged drug injection and S. mutans oral infection. Our findings may have important translational implications for the development of treatments for the management of METH mouth and more effective preventive public health strategies that can be applied to provide effective dental care for METH users in prisons, drug treatment centers, and health clinics.


Biologija ◽  
2020 ◽  
Vol 66 (3) ◽  
Author(s):  
Jana Radzijevskaja ◽  
Justina Snegiriovaitė ◽  
Artūras Kibiša ◽  
Irma Ražanskė ◽  
Algimantas Paulauskas

Anaplasma phagocytophilum is a bacterial pathogen, which is a major cause of zoonotic disease, anaplasmosis. The main vectors of A. phagocytophilum are ticks of the Ixodes ricinus complex. A. phagocytophilum has a broad geographic distribution and a high degree of biological and clinical diversity. Epidemiological studies in multiple countries have shown that the prevalence of A. phagocytophilum highly depends on the density of ticks and their potential hosts such as the cervids, which are one of the main sources of nutrition for Ixodes ticks. In Lithuania, the cervids are important game animals but their contribution as reservoirs for A. phagocytophilum remains unknown. The objectives of the study were to investigate the prevalence of A. phagocytophilum infections in the cervids and feeding ticks and to characterize the A. phagocytophilum strains obtained from the cervids and ticks based on sequence analysis of msp4 gene. A total of 187 ticks were collected from 44 cervids (roe deer, red deer, and moose) harvested by professional hunters during the hunting seasons of 2010–2013 and 2016–2017 in Lithuania. Blood and spleen samples were collected from 29 animals (27 roe deer and two red deer). A. phagocytophilum DNA was identified in ten (37.04%) of the 27 roe deer. The overall prevalence of A. phagocytophilum in I. ricinus and D. reticulatus ticks was 39.3% (70/178) and 22.2% (2/9) respectively. The sequence analysis of the msp4 gene of A. phagocytophilum revealed nine different sequence types: five msp4 sequence types were detected in ticks and seven in roe deer.


2014 ◽  
Vol 82 (5) ◽  
pp. 1968-1981 ◽  
Author(s):  
Megan L. Falsetta ◽  
Marlise I. Klein ◽  
Punsiri M. Colonne ◽  
Kathleen Scott-Anne ◽  
Stacy Gregoire ◽  
...  

ABSTRACTStreptococcus mutansis often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC).S. mutansmay not act alone;Candida albicanscells are frequently detected along with heavy infection byS. mutansin plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhancedin vitroandin vivo. The presence ofC. albicansaugments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viableS. mutanscells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeableS. mutansmicrocolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Ourin vitrodata also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence withC. albicansinduces the expression of virulence genes inS. mutans(e.g.,gtfB,fabM). We also found thatCandida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.


2009 ◽  
Vol 195 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Hannah Gardener ◽  
Donna Spiegelman ◽  
Stephen L. Buka

BackgroundThe aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years.AimsTo provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism.MethodPubMed, Embase and PsycINFO databases were searched for epidemiological studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies.ResultsOver 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born v. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, pre-eclampsia and swelling.ConclusionsThere is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.


1993 ◽  
Vol 73 (3_suppl) ◽  
pp. 1291-1298 ◽  
Author(s):  
Sally H. Rankin ◽  
Michael E. Galbraith ◽  
Sharon Johnson

A translated version of the CES-Depression scale attained a reliability coefficient alpha of 0.92 in a group of 30 adult Chinese persons with noninsulin-dependent diabetes mellitus. Fifteen percent of the sample scored 16 or above, which has been noted as indicative of depression in U.S. samples. The validity of the instrument was assessed through an in-depth content analysis and through convergent validity analyses. Comparison of depression scores of this sample with those from English-speaking Occidentals shows that diabetes disease-related factors may be an important influence on depression.


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