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Background: The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a proposed virulence factor of Ureaplasma spp. We previously demonstrated that the number of Ureaplasma parvum MBA size variants in amniotic fluid was inversely proportional to the severity of chorioamnionitis in experimentally infected pregnant sheep. However, the effect of ureaplasma MBA size variation on inflammation in human pregnancies has not been reported. Methods: Ureaplasmas isolated from the chorioamnion of pregnant women from a previous study (n = 42) were speciated/serotyped and MBA size variation was demonstrated by PCR and western blot. Results were correlated with the severity of chorioamnionitis and cord blood cytokines. In vitro, THP-1-derived macrophages were exposed to recombinant-MBA proteins of differing sizes and NF-κB activation and cytokine responses were determined. Results: MBA size variation was identified in 21/32 (65.6%) clinical isolates (in 10 clinical isolates MBA size variation was unable to be determined). Any size variation (increase/decrease) of the MBA (regardless of Ureaplasma species or serovar) was associated with mild or absent chorioamnionitis (P = 0.023) and lower concentrations of cord blood cytokines IL-8 (P = 0.04) and G-CSF (P = 0.008). In vitro, recombinant-MBA variants elicited different cytokine responses and altered expression of NF-κB p65. Conclusion: This study demonstrates that size variation of the ureaplasma MBA protein modulates the host immune response in vivo and in vitro.

Experimental sleep restriction (SR) has demonstrated reduced insulin sensitivity in healthy individuals. Exercise is well-known to be beneficial for metabolic health. A single bout of exercise has the capacity to increase insulin sensitivity for up to 2 days. Therefore, the current study aimed to determine if sprint interval exercise could attenuate the impairment in insulin sensitivity after one night of SR in healthy males. Nineteen males were recruited for this randomized crossover study which consisted of four conditions—control, SR, control plus exercise, and sleep restriction plus exercise. Time in bed was 8 hr (2300–0700) in the control conditions and 4 hr (0300–0700) in the SR conditions. Conditions were separated by a 1-week entraining period. Participants slept at home, and compliance was assessed using wrist actigraphy. Following the night of experimental sleep, participants either conducted sprint interval exercise or rested for the equivalent duration. An oral glucose tolerance test was then conducted. Blood samples were obtained at regular intervals for measurement of glucose and insulin. Insulin concentrations were higher in SR than control (p =.022). Late-phase insulin area under the curve was significantly lower in sleep restriction plus exercise than SR (862 ± 589 and 1,267 ± 558; p =.004). Glucose area under the curve was not different between conditions (p =.207). These findings suggest that exercise improves the late postprandial response following a single night of SR. [ABSTRACT FROM AUTHOR]

This article discusses the increasing resistance of Mycoplasma genitalium, a sexually transmitted infection, to antimicrobials in Queensland, Australia. The study examined samples collected between 2016 and 2021 and found that fluoroquinolone resistance mutations in the parC and gyrA genes were common, particularly the GyrA-M95I mutation. The presence of concurrent ParC-S83I and GyrA-M95I mutations was associated with lower cure rates with certain antibiotics. The study also identified specific genotypes of M. genitalium that were enriched with these resistant mutations, suggesting the circulation of highly resistant strains in large sexual networks. [Extracted from the article]

Mycoplasma hominis and Ureaplasma species infections in the post‐transplant setting are believed to be donor‐derived and can be associated with poor outcomes. Difficulty in culturing and identifying these organisms is a significant barrier to diagnosis and early intervention. Tetracyclines, macrolides and fluoroquinolones are the mainstay treatments to cure these infections; however, there are increasing reports of antibiotic resistance. In this case series, we report our single‐centre experience with M. hominis and U. urealyticum infection after lung transplantation (9 recipients, all men, mean age 56 years). Delayed diagnosis was common. Young donor age (mean age 23 yrs) and high‐risk donor social history (67%) were repeatedly noted in these cases, and all infections were associated with significant morbidity (anastomosis and sternal wound infection, empyema, mediastinitis, pericarditis). Two patients died; with one directly related to Ureaplasma urealyticum infection. In conclusion post lung transplant M. hominis, and U. urealyticum infections are challenging and carry high morbidity. More prospective studies are required to assess the true prevalence, full spectrum of complications and utility of molecular diagnostics to aid early diagnosis and identify antibiotic susceptibility of Mycoplasma and Ureaplasma infections in the post‐lung transplant setting. [ABSTRACT FROM AUTHOR]

Problem: HSV‐2 infected more than 491 million people aged 15–49 world‐wide in 2016. The morbidity associated with recurrent infections and the increased risk of HIV infection make this a major health problem. To date there is no effective vaccine. Because HSV‐2 ascends to the dorsal route ganglion within 12–18 h of infection, an effective vaccine will need to elicit a strong local resident CD8+ T cell response to prevent the infection from becoming life‐long. Method of Study: Using a mouse model we investigated the potential of oral immunization with a novel lipid adjuvant (LiporaleTM) followed by local vaginal application of an inflammatory agents to protect against primary HSV‐2 infections. Results: Oral vaccination of mice with live‐attenuated HSV‐2 in Liporale followed by vaginal application of DNFB or CXCL9/10 led to recruitment of tissue‐resident CD8+ memory cells into the genital epithelia. This prime and pull vaccination strategy provided complete protection against wild‐type HSV‐2 challenge and prevented viral dissemination to the spinal cords. Conclusions: Activation of mucosal immunity by oral immunization, combined with induction of transient local genital inflammation can recruit long‐lived tissue resident CD8+ T cells into the genital epithelium, providing significant protection against primary HSV‐2 infection. [ABSTRACT FROM AUTHOR]

Mycoplasma genitalium is an emerging sexually transmitted bacterium that is gaining attention because of the impact escalating antimicrobial resistance (AMR) is having on patient management. Of additional concern is that increased availability of testing appears to be resulting in screening practices that are not supported by clinical guidelines. This results in increasing numbers of asymptomatic M. genitalium infections being identified, which when combined with AMR issues, creates significant challenges for patients and clinicians. Rapidly rising levels of AMR, coupled with limited alternative treatment options, means patients can enter cycles of complex antimicrobial regimens that may cause more harm than the infection itself. In this review, we discuss the emergence of AMR and the implication for treatment practices, highlight the recommendations for testing but not screening for M. genitalium , and discuss expansion of individualised treatment strategies, to curb the emergence of resistance and improve outcomes for patients. We also provide suggestions for future research on the transmission and spread of resistance, to enhance global surveillance of this antimicrobial resistant pathogen and inform the revision of local and international treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma genitalium infections have rapidly become resistant to mainstay treatments. While individualised treatment approaches have improved treatment outcomes for macrolides, individualised therapy for fluoroquinolones has not yet been explored, due to scarcity of commercial assays and a lack of confidence in specific mutations associated with resistance. However, our recent work identified the diagnostic utility of targeting wildtype sequences to infer susceptibility to fluoroquinolones. This upends the conventional method of targeting resistance markers to infer resistance. Current suitable molecular methods are, however, lacking. This study aimed to develop and test proof-ofconcept molecular assays targeting the wildtype sequences of parC. Methods: Assays were designed to focus on detection of M. genitalium and characterisation of wildtype parC sequences, that are strongly linked with fluoroquinolone susceptibility. Targeting parC wildtype sequences are also simpler to design, such that samples containing sequences with a complete match to the wildtype probe will have identical melting peak temperatures, while any mismatches (including resistance mutations) result in significantly lower melting peak temperatures. These differences are easily differentiated for characterizing both ParC wildtype and mutants. Results: The method was validated using 227 M. genitalium-positive samples, and the results compared to DNA sequencing. These assays were able to detect M. genitalium and characterise fluoroquinolone susceptibility in 143/227 (63%) of samples. The majority of samples which were not able to be characterised often had very low M. genitalium microbial load. We saw 100% agreement between "gold standard" DNA sequencing and the results of our novel probe-based assays and there was a clear shift (decrease) in melting peak temperatures for samples harbouring ParC mutations linked with fluoroquinolone resistance. Conclusion: These proof-of-concept assays have considerable value to improve individualised treatment approaches and rationalize tests of cure for M. genitalium infections. The ability to initiate individualised treatment in up to two-thirds of cases will enhance antimicrobial stewardship for this challenging pathogen. [ABSTRACT FROM AUTHOR]