scholarly journals The Conserved Spore Coat Protein SpoVM Is Largely Dispensable in Clostridium difficile Spore Formation

mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
John W. Ribis ◽  
Priyanka Ravichandran ◽  
Emily E. Putnam ◽  
Keyan Pishdadian ◽  
Aimee Shen
Keyword(s):  
United States ◽  
Bacillus Subtilis ◽  
Clostridium Difficile ◽  
Diarrheal Disease ◽  
The United States ◽  
Spore Formation ◽  
Minor Role ◽  
Obligate Anaerobe ◽  
Content Type ◽  
A Minor

ABSTRACT The spore-forming obligate anaerobe Clostridium difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. When C. difficile spores are ingested by susceptible individuals, they germinate within the gut and transform into vegetative, toxin-secreting cells. During infection, C. difficile must also induce spore formation to survive exit from the host. Since spore formation is essential for transmission, understanding the basic mechanisms underlying sporulation in C. difficile could inform the development of therapeutic strategies targeting spores. In this study, we determine the requirement of the C. difficile homolog of SpoVM, a protein that is essential for spore formation in Bacillus subtilis due to its regulation of coat and cortex formation. We observed that SpoVM plays a minor role in C. difficile spore formation, in contrast with B. subtilis, indicating that this protein would not be a good target for inhibiting spore formation. The spore-forming bacterial pathogen Clostridium difficile is a leading cause of health care-associated infections in the United States. In order for this obligate anaerobe to transmit infection, it must form metabolically dormant spores prior to exiting the host. A key step during this process is the assembly of a protective, multilayered proteinaceous coat around the spore. Coat assembly depends on coat morphogenetic proteins recruiting distinct subsets of coat proteins to the developing spore. While 10 coat morphogenetic proteins have been identified in Bacillus subtilis, only two of these morphogenetic proteins have homologs in the Clostridia: SpoIVA and SpoVM. C. difficile SpoIVA is critical for proper coat assembly and functional spore formation, but the requirement for SpoVM during this process was unknown. Here, we show that SpoVM is largely dispensable for C. difficile spore formation, in contrast with B. subtilis. Loss of C. difficile SpoVM resulted in modest decreases (~3-fold) in heat- and chloroform-resistant spore formation, while morphological defects such as coat detachment from the forespore and abnormal cortex thickness were observed in ~30% of spoVM mutant cells. Biochemical analyses revealed that C. difficile SpoIVA and SpoVM directly interact, similarly to their B. subtilis counterparts. However, in contrast with B. subtilis, C. difficile SpoVM was not essential for SpoIVA to encase the forespore. Since C. difficile coat morphogenesis requires SpoIVA-interacting protein L (SipL), which is conserved exclusively in the Clostridia, but not the more broadly conserved SpoVM, our results reveal another key difference between C. difficile and B. subtilis spore assembly pathways. IMPORTANCE The spore-forming obligate anaerobe Clostridium difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. When C. difficile spores are ingested by susceptible individuals, they germinate within the gut and transform into vegetative, toxin-secreting cells. During infection, C. difficile must also induce spore formation to survive exit from the host. Since spore formation is essential for transmission, understanding the basic mechanisms underlying sporulation in C. difficile could inform the development of therapeutic strategies targeting spores. In this study, we determine the requirement of the C. difficile homolog of SpoVM, a protein that is essential for spore formation in Bacillus subtilis due to its regulation of coat and cortex formation. We observed that SpoVM plays a minor role in C. difficile spore formation, in contrast with B. subtilis, indicating that this protein would not be a good target for inhibiting spore formation.

scholarly journals Characterization of Clostridium difficile Spores Lacking Either SpoVAC or Dipicolinic Acid Synthetase

2016 ◽  
Vol 198 (11) ◽  
pp. 1694-1707 ◽  
Author(s):  
M. Lauren Donnelly ◽  
Kelly A. Fimlaid ◽  
Aimee Shen
Keyword(s):  
Clostridium Difficile ◽  
Heat Resistance ◽  
Spore Germination ◽  
Dipicolinic Acid ◽  
The United States ◽  
Spore Formation ◽  
Obligate Anaerobe ◽  
Wild Type ◽  
Content Type ◽  
Wet Heat

ABSTRACTThe spore-forming obligate anaerobeClostridium difficileis a leading cause of antibiotic-associated diarrhea around the world. In order forC. difficileto cause infection, its metabolically dormant spores must germinate in the gastrointestinal tract. During germination, spores degrade their protective cortex peptidoglycan layers, release dipicolinic acid (DPA), and hydrate their cores. InC. difficile, cortex hydrolysis is necessary for DPA release, whereas inBacillus subtilis, DPA release is necessary for cortex hydrolysis. Given this difference, we tested whether DPA synthesis and/or release was required forC. difficilespore germination by constructing mutations in eitherspoVACordpaAB, which encode an ion channel predicted to transport DPA into the forespore and the enzyme complex predicted to synthesize DPA, respectively.C. difficilespoVACanddpaABmutant spores lacked DPA but could be stably purified and were more hydrated than wild-type spores; in contrast,B. subtilisspoVACanddpaABmutant spores were unstable. AlthoughC. difficilespoVACanddpaABmutant spores exhibited wild-type germination responses, they were more readily killed by wet heat. Cortex hydrolysis was not affected by this treatment, indicating that wet heat inhibits a stage downstream of this event. Interestingly,C. difficilespoVACmutant spores were significantly more sensitive to heat treatment thandpaABmutant spores, indicating that SpoVAC plays additional roles in conferring heat resistance. Taken together, our results demonstrate that SpoVAC and DPA synthetase controlC. difficilespore resistance and reveal differential requirements for these proteins among theFirmicutes.IMPORTANCEClostridium difficileis a spore-forming obligate anaerobe that causes ∼500,000 infections per year in the United States. Although spore germination is essential forC. difficileto cause disease, the factors required for this process have been only partially characterized. This study describes the roles of two factors, DpaAB and SpoVAC, which control the synthesis and release of dipicolinic acid (DPA), respectively, from bacterial spores. Previous studies of these proteins in other spore-forming organisms indicated that they are differentially required for spore formation, germination, and resistance. We now show that the proteins are dispensable forC. difficilespore formation and germination but are necessary for heat resistance. Thus, our study further highlights the diverse functions of DpaAB and SpoVAC in spore-forming organisms.

scholarly journals Comparison of Multilocus Sequence Typing and the Xpert C. difficile/Epi Assay for Identification of Clostridium difficile 027/NAP1/BI

2015 ◽  
Vol 54 (3) ◽  
pp. 775-778 ◽  
Author(s):  
Tracy McMillen ◽  
Mini Kamboj ◽  
N. Esther Babady
Keyword(s):  
United States ◽  
Clostridium Difficile ◽  
Confidence Interval ◽  
Multilocus Sequence Typing ◽  
The United States ◽  
Content Type ◽  
Presumptive Identification ◽  
Good Agreement

Clostridium difficile027/NAP1/BI is the most commonC. difficilestrain in the United States. The XpertC. difficile/Epi assay allows rapid, presumptive identification ofC. difficileNAP1. We compared XpertC. difficile/Epi to multilocus sequence typing for identification ofC. difficileNAP1 and found “very good” agreement at 97.9% (κ = 0.86; 95% confidence interval, 0.80 to 0.91).

India-US ties will be sound but susceptible to shocks

2019 ◽  
Keyword(s):  
United States ◽  
Foreign Minister ◽  
The United States ◽  
Content Type ◽  
Economic Relations ◽  
A Minor

Subject Political and economic relations between Delhi and Washington. Significance Indian Foreign Minister Subrahmanyam Jaishankar last week said Delhi and Washington faced a challenge to “refresh” bilateral ties, despite “dramatic changes” over the last 20 years. India and the United States are strategic partners, but relations have come under strain over Kashmir, defence and trade. Impacts The recent halting of US-Taliban talks, which had worried Delhi because they excluded Kabul, will remove a minor source of India-US tension. India-US commercial spats will hurt Delhi’s ‘Make in India’ scheme, designed to persuade international manufactures to seek local partners. Enduring India-US strains would undermine Washington’s Indo-Pacific strategy, as Delhi is a key partner within it.

Political Science in the United States in Wartime

1947 ◽  
Vol 41 (5) ◽  
pp. 978-989
Author(s):  
Carl J. Friedrich
Keyword(s):  
United States ◽  
Political Science ◽  
Political Institutions ◽  
Professional Training ◽  
The United States ◽  
Minor Role ◽  
International Affairs ◽  
Special Schools ◽  
European Universities ◽  
A Minor

The field known as “political science” is in many ways a peculiarly American discipline. Although it plays a minor rôle in some European universities, and none in the rest, this particular field of the social sciences is of great importance in the United States. Besides a mounting interest in the study of government on the undergraduate level in this country, there has been a steady growth of professional training for the public service in special schools of public administration and in international affairs and diplomacy, both closely related to and usually staffed in part at least by political scientists.To the non-American inquiring as to the reason for this special development, no exhaustive answer can be given at the present time. But mention may be made of a number of factors which have contributed to this phenomenal and persistent growth. In the first place, political science, backed by the ancient tradition of Aristotle's Politics, has a central appeal to young men and women seeking an integrated and over-all approach to the “great society” of a free and intensely democratic people. The pride Americans used to take in their political “institutions,” which was noted by many a foreign traveller, has in this age of democratic disillusionment found an uneasy refuge in academic study of the history of political thought and institutions. The well-known practical, or rather activist, tendency of American scholars has turned many an economist, such as John R. Commons, to legislative halls and thus has pushed the problems of government into the center of attention. Historians with similar propensities, like Charles A. Beard, came to enrich the work of political science.

scholarly journals The Gut Microbiota Is Associated with Clearance ofClostridium difficileInfection Independent of Adaptive Immunity

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Jhansi L. Leslie ◽  
Kimberly C. Vendrov ◽  
Matthew L. Jenior ◽  
Vincent B. Young
Keyword(s):  
United States ◽  
Immune Response ◽  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Adaptive Immunity ◽  
Adaptive Immune Response ◽  
The United States ◽  
Content Type ◽  
Adaptive Immune

ABSTRACTClostridium(Clostridioides)difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor forClostridium difficileinfection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance ofC. difficilehas yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance ofC. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance ofC. difficilefrom the murine gastrointestinal tract.IMPORTANCEClostridium difficileinfection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels ofC. difficilecolonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance ofC. difficilefrom the GI tract. Our results show that clearance ofC. difficilecan occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.

scholarly journals The Political Context and Infant Health in the United States

2021 ◽  
Author(s):  
Florencia Torche ◽  
Tamkinat Rauf
Keyword(s):  
United States ◽  
Beneficial Effect ◽  
Population Health ◽  
Fixed Effects ◽  
Infant Health ◽  
The United States ◽  
Political Context ◽  
Minor Role ◽  
A Minor ◽  
Future Population

Most social determinants of health are shaped by political decisions. However, beyond specific policies, there is limited empirical investigation into the consequences of the changing political context on population health in the United States. We examine a salient political factor—the party of the president and governor—as a determinant of infant health between 1971 and 2018 using a battery of fixed-effects models. We focus on infant health because it has far-reaching implications for future population health and inequality. Our analysis yields three findings: (1) Democratic presidents have a beneficial effect on infant health outcomes, with stronger effects for Black infants compared to White infants. (2) The president’s party effect materializes after two years of a Democratic transition and remains elevated until the end of the party’s tenure in office. (3) Specific measurable social policies appear to play a minor role in explaining the beneficial effect of Democratic administrations. Our findings suggest the party in power is an important determinant of infant health, particularly among vulnerable populations, and they invite a deeper examination of mechanisms.

scholarly journals The Political Context and Infant Health in the United States

2021 ◽  
pp. 000312242110007
Author(s):  
Florencia Torche ◽  
Tamkinat Rauf
Keyword(s):  
United States ◽  
Beneficial Effect ◽  
Population Health ◽  
Fixed Effects ◽  
Infant Health ◽  
The United States ◽  
Political Context ◽  
Minor Role ◽  
A Minor ◽  
Future Population

Most social determinants of health are shaped by political decisions. However, beyond specific policies, there is limited empirical investigation into the consequences of the changing political context on population health in the United States. We examine a salient political factor—the party of the president and governor—as a determinant of infant health between 1971 and 2018 using a battery of fixed-effects models. We focus on infant health because it has far-reaching implications for future population health and inequality. Our analysis yields three findings: (1) Democratic presidents have a beneficial effect on infant health outcomes, with stronger effects for Black infants compared to White infants. (2) The president’s party effect materializes after two years of a Democratic transition, and remains elevated until the end of the party’s tenure in office. (3) Specific measurable social policies appear to play a minor role in explaining the beneficial effect of Democratic administrations. Our findings suggest the party in power is an important determinant of infant health, particularly among vulnerable populations, and they invite a deeper examination of mechanisms.

scholarly journals Evidence that Cryptosporidium parvum Populations Are Panmictic and Unstructured in the Upper Midwest of the United States

2012 ◽  
Vol 78 (22) ◽  
pp. 8096-8101 ◽  
Author(s):  
Grant R. Herges ◽  
Giovanni Widmer ◽  
Mark E. Clark ◽  
Eakalak Khan ◽  
Catherine W. Giddings ◽  
...  
Keyword(s):  
United States ◽  
Cryptosporidium Parvum ◽  
Diarrheal Disease ◽  
Protozoan Parasite ◽  
The United States ◽  
Multilocus Genotype ◽  
Upper Midwest ◽  
Content Type ◽  
Midwest United States ◽  
Diarrheic Calves

ABSTRACTCryptosporidium parvumis a zoonotic protozoan parasite that causes cryptosporidiosis, an infectious diarrheal disease primarily affecting humans and neonatal ruminants. Understanding the transmission dynamics ofC. parvum, particularly the specific contributions of zoonotic and anthroponotic transmission, is critical to the control of this pathogen. This study used a population genetics approach to better understand the transmission ofC. parvumin the Upper Midwest United States. A total of 254C. parvumisolates from cases of human cryptosporidiosis in Minnesota and Wisconsin and diarrheic calves in Minnesota, Wisconsin, and North Dakota were genotyped at eight polymorphic loci. Isolates with a complete profile from all eight loci (n= 212) were used to derive a multilocus genotype (MLT), which was used in population genetic analyses. Among the 94 MLTs identified, 60 were represented by a single isolate. Approximately 20% of isolates belonged to MLT 2, a group that included both human and cattle isolates. Population analyses revealed a predominantly panmictic population with no apparent geographic or host substructuring.

scholarly journals The Structure of a Never Regulated Less-Than-Truckload Market in the United States

1987 ◽  
Vol 16 (2) ◽  
pp. 113-122
Author(s):  
Richard Beilock ◽  
Mohammed Rahmani ◽  
Mercedes Rosalsky
Keyword(s):  
United States ◽  
The United States ◽  
Minor Role ◽  
Regulated Markets ◽  
Long Run ◽  
Economies Of Size ◽  
A Minor ◽  
Concentration Ratios

The structure of the never-regulated, less-than-truckload transport market for Florida ornamentals is examined using concentration ratios, and the Hirchman-Herfindahl, Rosenbluth, and E Indices. The results indicate that this market is not highly concentrated relative to all US markets or to regulated trucking markets. This suggests that the long run structure of the trucking markets where regulations have been relaxed will not be highly concentrated and that economies of size may not be large. It was also found that, despite characteristics favorable to own-account carriage, it plays a minor role in ornamentals transportation relative to in regulated markets. This is consistent with the hypothesis that avoidance of problems and costs related to regulated carriage can be an incentive for firms to adopt own-account carriage.

scholarly journals Strain Types and Antimicrobial Resistance Patterns of Clostridium difficile Isolates from the United States, 2011 to 2013

2014 ◽  
Vol 58 (7) ◽  
pp. 4214-4218 ◽  
Author(s):  
Isabella A. Tickler ◽  
Richard V. Goering ◽  
Joseph D. Whitmore ◽  
Ashley N. W. Lynn ◽  
David H. Persing ◽  
...  
Keyword(s):  
United States ◽  
Clostridium Difficile ◽  
Antimicrobial Resistance ◽  
Antimicrobial Susceptibility ◽  
The United States ◽  
Geographic Region ◽  
Content Type ◽  
Resistance Patterns ◽  
Strain Type ◽  
Susceptibility Patterns

ABSTRACTWe determined the PCR ribotypes and antimicrobial susceptibility patterns of 508 toxigenicClostridium difficileisolates collected between 2011 and 2013 from 32 U.S. hospitals. Of the 29 PCR ribotypes identified, the 027 strain type was the most common (28.1%), although the rates varied by geographic region. Ribotype 014/020 isolates appear to be emerging. Clindamycin and moxifloxacin resistances (36.8% and 35.8%, respectively) were the most frequent resistance phenotypes observed. Reduced susceptibility to vancomycin was observed in 39.1% of 027 isolates.

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