Sporulation and Germination in Clostridial Pathogens

Shen, Aimee; Edwards, Adrianne N.; Sarker, Mahfuzur R.; Paredes-Sabja, Daniel

doi:10.1128/microbiolspec.gpp3-0017-2018

Cited by 89 publications

(68 citation statements)

References 283 publications

(531 reference statements)

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“…DPA is made in the mother cell compartment of the sporulating cell, and imported into developing spores probably as CaDPA via several spore-specific channels (Ramírez-Guadiana et al, 2017;Setlow and Johnson, 2019); this incorporation almost certainly requires energy and lowers the spore core water content appreciably. CaDPA also has roles in spore resistance, is rapidly released during spore germination, and has a signaling role in germination of spores of most, but probably not all Firmicutes (Setlow et al, 2017;Shen et al, 2019).…”

Section: The Early Yearsmentioning

confidence: 99%

“…Spores are formed by some Firmicutes species, the most wellstudied being those of the Bacillales, although studies on spores of Clostridiales species are increasing (Tan and Ramamurthi, 2014;Setlow and Johnson, 2019;Shen et al, 2019). Such spores are considered metabolically dormant and extremely resistant to all manner of potentially harmful treatments, including wet and dry heat, desiccation, high radiation levels, and a host of toxic chemicals, including antibiotics, and can survive for many years (Setlow, 2006;Ulrich et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Notably, dormant spores' central core (Figure 1), comparable to the protoplast of a growing cell, has an extremely low water content, as low as 25% of wet wt in spores of some thermophiles and 35% of wet wt in the well-studied Bacillus subtilis spores; this is in contrast to the value of 80% of wet wt as water in growing cells or fully germinated spores (Gerhardt and Marquis, 1989). Spores have been studied in part because of their fascinating life cycle of growth, sporulation, and spore germination (Tan and Ramamurthi, 2014;Setlow et al, 2017;Shen et al, 2019). In addition, spores of a number of species are vectors for human diseases or intoxications, as well as food spoilage and food-borne disease.…”

Section: Introductionmentioning

confidence: 99%

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Bacterial Spore mRNA – What’s Up With That?

Setlow

Christie

2020

Front. Microbiol.

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Bacteria belonging to the orders Bacillales and Clostridiales form spores in response to nutrient starvation. From a simplified morphological perspective, the spore can be considered as comprising a central protoplast or core, that is, enveloped sequentially by an inner membrane (IM), a peptidoglycan cortex, an outer membrane, and a proteinaceous coat. All of these structures are characterized by unique morphological and/or structural features, which collectively confer metabolic dormancy and properties of environmental resistance to the quiescent spore. These properties are maintained until the spore is stimulated to germinate, outgrow and form a new vegetative cell. Spore germination comprises a series of partially overlapping biochemical and biophysical events-efflux of ions from the core, rehydration and IM reorganization, disassembly of cortex and coat-all of which appear to take place in the absence of de novo ATP and protein synthesis. If the latter points are correct, why then do spores of all species examined to date contain a diverse range of mRNA molecules deposited within the spore core? Are some of these molecules "functional," serving as translationally active units that are required for efficient spore germination and outgrowth, or are they just remnants from sporulation whose sole purpose is to provide a reservoir of ribonucleotides for the newly outgrowing cell? What is the fate of these molecules during spore senescence, and indeed, are conditions within the spore core likely to provide any opportunity for changes in the transcriptional profile of the spore during dormancy? This review encompasses a historical perspective of spore ribonucleotide biology, from the earliest biochemical led analyses-some of which in hindsight have proved to be remarkably prescient-through the transcriptomic era at the turn of this century, to the latest next generation sequencing derived insights. We provide an overview of the key literature to facilitate reasoned responses to the aforementioned questions, and many others, prior to concluding by identifying the major outstanding issues in this crucial area of spore biology.

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Section: The Early Yearsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bacterial Spore mRNA – What’s Up With That?

Setlow

Christie

2020

Front. Microbiol.

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“…A C. perfringens F-típusa (korábban A-típusa) okozhat élelmiszer-eredetű és nem élelmiszer-eredetű gastrointestinalis megbetegedést. A tüneteket a CPE-toxin idézi elő, amely vagy a kromoszóma cpe-génjén, vagy egy plazmidon kódolódik [29]. A cpe-gént a C-, a D-és az E-törzs is kódolja [27].…”

Section: Clostridium Perfringensunclassified

Élelmiszer eredetű bakteriális megbetegedések patogenezise, klinikai jellegzetességei, diagnosztikája és kezelése

Müller

Rozgonyi

2020

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Összefoglaló. Az élelmiszer-eredetű megbetegedések igen gyakoriak, bár pontos adatok nem állnak rendelkezésre, mivel az enyhe, gyorsan múló gastrointestinalis tünetekkel a betegek nem fordulnak orvoshoz, vagy nem történik diagnosztikus vizsgálat. Az amerikai Járványügyi és Betegségmegelőzési Központ (CDC) adatai szerint az USA-ban évente 6 lakosból 1 esik át élelmiszer okozta tüneteken. Az ételintoxikációk során a baktérium által termelt toxinok okozzák a tüneteket, közülük a leggyakoribb a Clostridium perfringens, a Staphylococcus aureus és a Bacillus cereus okozta, élelmiszer-eredetű intoxikáció. A nem megfelelően tárolt vagy hőkezelt élelmiszerekben – beleértve a S. aureus által szennyezett anyatejet – ezen baktériumok életképesek maradnak, elszaporodnak, és toxint termelhetnek, illetve toxinjaik megőrzik megbetegítőképességüket. Az étel elfogyasztása után 3–12 órával hányást, hasmenést okoznak. A tünetek többnyire 24 órán belül megszűnnek. A Clostridium botulinum súlyos neurológiai tünetei miatt emelkedik ki a többi toxikoinfekció sorából. C. botulinum okozta tünetekre felnőtteknél házi készítésű konzervek és húskészítmények elfogyasztása után jelentkező gastrointestinalis vagy neurológiai tünetek esetén kell gondolnunk. A Clostridioides difficile szintén a toxinjai révén okoz súlyos, életveszélyes megbetegedést, továbbá az esetek 20–30%-ában számolnunk kell az infekció relapsusával. Növekvő gyakorisága miatt ismernünk érdemes a laboratóriumi és klinikai diagnosztika részleteit és a legmodernebb kezelési lehetőségeket, úgymint megfelelő mintavétel, mintatárolás és -szállítás, tenyésztés, toxinkimutatás, helyes tüneti kezelés, antibiotikumkombinációk, széklettranszplantáció és monoklonálisantitest-kezelés. Orv Hetil. 2020; 161(48): 2019–2028. Summary. Foodborne diseases are quite common, however, accurate data are not available because patients do not visit doctors with mild, rapidly resolving symptoms and diagnostic tests are not performed. The Centers of Disease Control and Prevention (CDC) estimates that, in the USA, 1 in 6 citizens gets food poisoning yearly. Symptoms of intoxication are due to the toxins produced by bacteria, mostly by Clostridium perfringens, Staphylococcus aureus and Bacillus cereus. These bacteria can survive in not properly stored or heated food, including S. aureus contaminated breastmilk. They can multiply and produce toxins causing intoxications. The gastrointestinal symptoms start 3–12 hours after consumption of the contaminated food and resolve in 24 hours. Clostridium botulinum causes severe neurological symptoms that should be suspected after consumption of home-made cans, smoked hams and sausages. The disease caused by Clostridioides difficile is not a foodborne one, but C. difficile causes severe infection via its toxins. Another problem is that C. difficile infection recurs in 20–30% of cases. Due to the increasing incidence of foodborne diseases, it is worth to learn the precise clinical and laboratory diagnostic algorithms including sampling, storage and transportation of samples, cultivation of bacteria and differential diagnosis of these diseases, furthermore the most up-to-date symptomatic and causative treatment options like antibiotic combinations, stool transplantation and monoclonal antibodies. Orv Hetil. 2020; 161(48): 2019–2028.

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“…C. difficile infections begin when its metabolically dormant spore form germinates in the gut of vertebrate hosts in response to certain bile acids [22]. Notably, these bile acid germinants differ from the nutrient germinants sensed by almost all other spore-formers studied to date, and their signal transduction mechanism appears to be unique because C. difficile lacks the transmembrane germinant receptors found in all other spore formers [23][24][25][26]. Instead, the bile acid germinant signal is transduced by members of the clostridial serine protease family known as the Csps [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Differential effects of ‘resurrecting' Csp pseudoproteases during Clostridioides difficile spore germination

Donnelly

Forster

Rohlfing

et al. 2020

Biochemical Journal

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Clostridioides difficile is a spore-forming bacterial pathogen that is the leading cause of hospital-acquired gastroenteritis. C. difficile infections begin when its spore form germinates in the gut upon sensing bile acids. These germinants induce a proteolytic signaling cascade controlled by three members of the subtilisin-like serine protease family, CspA, CspB, and CspC. Notably, even though CspC and CspA are both pseudoproteases, they are nevertheless required to sense germinants and activate the protease, CspB. Thus, CspC and CspA are part of a growing list of pseudoenzymes that play important roles in regulating cellular processes. However, despite their importance, the structural properties of pseudoenzymes that allow them to function as regulators remain poorly understood. Our recently solved crystal structure of CspC revealed that its pseudoactive site residues align closely with the catalytic triad of CspB, suggesting that it might be possible to ‘resurrect' the ancestral protease activity of the CspC and CspA pseudoproteases. Here, we demonstrate that restoring the catalytic triad to these pseudoproteases fails to resurrect their protease activity. We further show that the pseudoactive site substitutions differentially affect the stability and function of the CspC and CspA pseudoproteases: the substitutions destabilized CspC and impaired spore germination without affecting CspA stability or function. Thus, our results surprisingly reveal that the presence of a catalytic triad does not necessarily predict protease activity. Since homologs of C. difficile CspA occasionally carry an intact catalytic triad, our results indicate that bioinformatic predictions of enzyme activity may underestimate pseudoenzymes in rare cases.

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Sporulation and Germination in Clostridial Pathogens

Cited by 89 publications

References 283 publications

Bacterial Spore mRNA – What’s Up With That?

Bacterial Spore mRNA – What’s Up With That?

Élelmiszer eredetű bakteriális megbetegedések patogenezise, klinikai jellegzetességei, diagnosztikája és kezelése

Differential effects of ‘resurrecting' Csp pseudoproteases during Clostridioides difficile spore germination

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