Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group B Streptococcus.

Streptococcus agalactiae is among the few pathogens that have not developed resistance to ß-lactam antibiotics despite decades of clinical use. The molecular basis of this long-lasting susceptibility has not been investigated, and it is not known whether specific mechanisms constrain the emergence of resistance. In this study, we first report ß-lactam tolerance due to the inactivation of the c-di-AMP phosphodiesterase GdpP. Mechanistically, tolerance depends on antagonistic regulation by the repressor BusR, which is activated by c-di-AMP and negatively regulates ß-lactam susceptibility through the BusAB osmolyte transporter and the AmaP/Asp23/GlsB cell envelope stress complex. The BusR transcriptional response is synergistic with the simultaneous allosteric inhibition of potassium and osmolyte transporters by c-di-AMP, which individually contribute to low-level ß-lactam tolerance. Genome-wide transposon mutagenesis confirms the role of GdpP and highlights functional interactions between a lysozyme-like hydrolase, the KhpAB RNA chaperone and the protein S immunomodulator in the response of GBS to ß-lactam. Overall, we demonstrate that c-di-AMP acts as a turgor pressure rheostat, coordinating an integrated response at the transcriptional and post-translational levels to cell wall weakening caused by ß-lactam activity, and reveal additional mechanisms that could foster resistance.

Recurrent Group B Streptococcus neonatal invasive infections, France, 2007 -2021.

Recurrence is a rare complication of Group B Streptococcus (GBS) neonatal infections. We conducted a retrospective observational study on GBS neonatal invasive infections in France from 2007 to 2021. 1,527 cases were reported, of which 36 (2.36%) were recurrent. Recurrence mainly concerned preterm (68%) and low birthweight (72%) infants and was associated with the hypervirulent GBS clonal complex 17 (83%, OR 2.86, 95% CI 1.18-6.92). No beta-lactam tolerant strains were identified and bacterial whole genome sequencing could not reveal any specific feature associated with recurrence. Large cohort studies should be undertaken to address the optimal management of these uncommon diseases.

Performances of two rapid LAMP-based techniques for the intrapartum detection of Group B Streptococcus vaginal colonization.

PURPOSE: Group B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid intrapartum detection of GBS vaginal colonization using real-time nucleic acid amplification tests (NAATs) emerged as an alternative to antenatal culture screening methods. METHODS: We compared the performances of two loop-mediated isothermal amplification (LAMP) tests, the Ampliflash® GBS and the PlusLife® GBS tests, to standard culture for GBS detection in vaginal specimens from pregnant women. The study was conducted from April to July 2023 in a French hospital of the Paris area. RESULTS: A total of 303 samples were analyzed, including 85 culture-positive samples (28.1%). The Ampliflash® GBS test and the PlusLife® GBS tests gave a result for 100% and 96.3% tests, respectively. The performances of the tests were as follows: sensitivity 87.1% (95% confidence interval (CI) 78.3-92.6) and 98.7% (95% CI 93.0-99.8), specificity 99.1% (95% CI 96.7-99.8), and 91.9% (95% CI 87.3-95.0), respectively. False negative results of the Ampliflash® GBS test correlated with low-density GBS cultures. Time-to-results correlated with GBS culture density only for the PlusLife® GBS test (p < 0.001). CONCLUSION: Both techniques provide excellent analytical performances with high sensitivity and specificity together with a short turnaround time and results available in 10 to 35 min. Their potential to further reduce the burden of GBS neonatal disease compared with antenatal culture screening needs to be assessed in future clinical studies.

Outbreak of group B Streptococcus in a neonatal care unit confirmed by whole-genome sequencing.

AIM: Clusters of group B Streptococcus (GBS) infections in neonatal intensive care units (NICU) are poorly documented. We aimed to assess GBS cross-transmission during an outbreak of GBS sepsis. METHODS: The study was carried out between October and November 2021 in a French University Hospital. Neonatal intensive care unit (NICU) patients with GBS sepsis were included. Clinical data were retrieved from electronic patient records. Group B Streptococcus isolates were characterized at the molecular level using capsular genotyping and whole-genome sequencing (WGS). RESULTS: The outbreak of GBS sepsis affected three very preterm neonates with a gestational age of less than 26 weeks, including one recurrent male index case aged 26 days, and two female secondary cases aged 5 and 17 days. The microbiological investigation identified a GBS isolate of capsular type III and Sequence Type 17 as responsible for the four infectious episodes. Whole-genome sequencing confirmed the identity between the isolates. The outbreak and the results of the microbiological investigations led to an immediate reinforcement of hygiene measures. CONCLUSION: Clustered cases of GBS infections in NICU and horizontal transmission of the hypervirulent GBS Sequence Type 17 are likely underestimated. Prospective investigation of all nosocomial cases using WGS should contribute to improving vigilance regarding GBS cross-transmission and infection prevention.

Can Chatbot Artificial Intelligence Replace Infectious Diseases Physicians in the Management of Bloodstream Infections? A Prospective Cohort Study.

BACKGROUND: The development of chatbot artificial intelligence (AI) has raised major questions about their use in healthcare. We assessed the quality and safety of the management suggested by Chat Generative Pre-training Transformer 4 (ChatGPT-4) in real-life practice for patients with positive blood cultures. METHODS: Over a 4-week period in a tertiary care hospital, data from consecutive infectious diseases (ID) consultations for a first positive blood culture were prospectively provided to ChatGPT-4. Data were requested to propose a comprehensive management plan (suspected/confirmed diagnosis, workup, antibiotic therapy, source control, follow-up). We compared the management plan suggested by ChatGPT-4 with the plan suggested by ID consultants based on literature and guidelines. Comparisons were performed by 2 ID physicians not involved in patient management. RESULTS: Forty-four cases with a first episode of positive blood culture were included. ChatGPT-4 provided detailed and well-written responses in all cases. AI's diagnoses were identical to those of the consultant in 26 (59%) cases. Suggested diagnostic workups were satisfactory (ie, no missing important diagnostic tests) in 35 (80%) cases; empirical antimicrobial therapies were adequate in 28 (64%) cases and harmful in 1 (2%). Source control plans were inadequate in 4 (9%) cases. Definitive antibiotic therapies were optimal in 16 (36%) patients and harmful in 2 (5%). Overall, management plans were considered optimal in only 1 patient, as satisfactory in 17 (39%), and as harmful in 7 (16%). CONCLUSIONS: The use of ChatGPT-4 without consultant input remains hazardous when seeking expert medical advice in 2023, especially for severe IDs.

Oxygen concentration modulates colibactin production.

Up to 25% of the E. coli strains isolated from the feces of healthy humans harbor the pks genomic island encoding the synthesis of colibactin, a genotoxic metabolite. Evidence is accumulating for an etiologic role of colibactin in colorectal cancer. Little is known about the conditions of expression of colibactin in the gut. The intestine is characterized by a unique oxygenation profile, with a steep gradient between the physiological hypoxic epithelial surface and the anaerobic lumen, which favors the dominance of obligate anaerobes. Here, we report that colibactin production is maximal under anoxic conditions and decreases with increased oxygen concentration. We show that the aerobic respiration control (ArcA) positively regulates colibactin production and genotoxicity of pks+ E. coli in response to oxygen availability. Thus, colibactin synthesis is inhibited by oxygen, indicating that the pks biosynthetic pathway is adapted to the anoxic intestinal lumen and to the hypoxic infected or tumor tissue.