Clostridium septicum manifests a bile salt germinant response mediated by Clostridioides difficile csp gene orthologs.

Clostridium septicum infections are highly predictive of certain malignancies in human patients. To initiate infections, C. septicum spores must first germinate and regain vegetative growth. Yet, what triggers the germination of C. septicum spores is still unknown. Here, we observe that C. septicum germinates in response to specific bile salts. Putative bile salt recognition genes are identified in C. septicum based on their similarity in sequence and organization to bile salt-responsive csp genes in Clostridioides difficile. Inactivating two of these csp orthologs (cspC-82 and cspC-1718) results in mutant spores that no longer germinate in the presence of their respective cognate bile salts. Additionally, inactivating the putative cspBA or sleC genes in C. septicum abrogates the germination response to all bile salt germinants, suggesting that both act at a convergent point downstream of cspC-82 and cspC-1718. Molecular dynamics simulations show that both CspC-82 and CspC-1718 bear a strong structural congruence with C. difficile's CspC. The existence of functional bile salt germination sensors in C. septicum may be relevant to the association between infection and malignancy.

Geospatial mapping of 2-hour access to timely essential surgery in the Philippines.

OBJECTIVES: Timely access to safe and affordable surgery is essential for universal health coverage. To date, there are no studies evaluating 2-hour access to Bellwether procedures (caesarean section, laparotomy, open fracture management) in the Philippines. The objectives of this study were to measure the proportion of the population able to reach a Bellwether hospital within 2 hours in the Philippines and to identify areas in the country with the most surgically underserved populations. METHODS: All public hospitals with Bellwether capacities were identified from the Philippines Ministry of Health website. The service area tool in ArcGIS Pro was used to determine the population within a 2-hour drive time of a Bellwether facility. Finally, suitability modelling was conducted to identify potential future sites for a surgical facility that targets the most underserved regions in the Philippines. RESULTS: 428 Bellwether capable hospitals were identified. 85.1% of the population lived within 2 hours of one of these facilities. However, 6 regions had less than 80% of its population living within 2 hours of a Bellwether capable facility: Bicol, Eastern Visayas, Zamboanga, Autonomous region of Muslim Mindanao, Caraga and Mimaropa. Suitability analysis identified four regions-Caraga, Mimaropa, Calabarzon and Zamboanga-as ideal locations to build a new hospital with surgical capacity to improve access rates. CONCLUSION: 85.1% of the population of the Philippines are able to reach Bellwether capable hospitals within 2 hours, with regional disparities in terms of access rates. However, other factors such as weather, traffic conditions, financial access, availability of 24-hour surgical services and access to motorised vehicles should also be taken into consideration, as they also affect actual access rates.