Epigenetic reprogramming of myeloid cells by infection or vaccination, termed trained immunity, confers non-specific protection from secondary infections. We characterized genome-wide transcriptome and histone modification profiles of human monocytes trained with β-glucan and identified induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, lactate production, and NAD+/NADH ratio, reflecting a shift in the metabolism of trained monocytes with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1/Akt/HIF1α pathway. Inhibition of Akt, mTOR, or HIF1α blocked monocyte induction of trained immunity, whereas the AMPK activator metformin inhibited the innate immune response to fungal infection. Finally, mice with a myeloid cell-specific defect in HIF1α were unable to mount trained immunity against bacterial sepsis. In conclusion, Akt/mTOR/HIF1α-dependent induction of aerobic glycolysis represents the metabolic basis of trained immunity.

Objectives. Neisseria gonorrhoeae antimicrobial drug resistance has emerged worldwide, however, the situation in Sub-Saharan Africa is not well-documented. We investigated the molecular epidemiology and occurrence of antimicrobial resistance in Neisseria gonorrhoeae infections in two core transmission groups of men in Johannesburg, South Africa. Methods. We recruited men who have sex with men (MSM) presenting with urethral discharge and men with a recurrent episode of urethral discharge. Molecular testing and culture for N. gonorrhoeae followed by antimicrobial susceptibility testing was performed. Whole genome sequencing (WGS) was used to identify resistance conferring mutations and to determine genetic relatedness of the isolates. Results. Fifty-one men were recruited; 42 (82%) had N. gonorrhoeae infection. Most gonococcal isolates were resistant to ciprofloxacin (78%) and tetracycline (74%); 33% were penicillin resistant. All gonococcal isolates were susceptible to cephalosporines and spectinomycin. Azithromycin resistance was observed in four (15%) isolates (epidemiological cut-off); all with mutations in the mtrR promoter region. Most of the isolates (19/27) harboured the gonococcal genetic island; associated with antimicrobial resistance. WGS revealed a diverse epidemic with mostly novel NG-STAR (70%) and NG-MAST (70%) sequence types. Conclusions. We demonstrate high prevalence of antimicrobial-resistance in Neisseria gonorrhoeae strains obtained from high-risk men in South Africa. Introduction of diagnostics and scale-up of surveillance are warranted to prevent emergence of multidrug-resistant infections.

There has been a growing body of evidence that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) shows enhanced transmissibility and increased viral loads compared to other variants. A recent study has even suggested that respiratory samples from people infected with the Delta variant can harbor up to 1000 times higher viral loads compared to samples with variants that are more closely related to the original Wuhan strain, although the sample size of this study (n = 125) was very limited. Here, we have compared the viral load in 16,185 samples that were obtained in periods during which non-VOC, the Alpha (B.1.1.7) or Delta variant (B.1.617.2) were dominant as evidenced by genomic surveillance. We found that the Delta variant contained about fourfold higher viral loads across all age groups compared to the non-VOC or Alpha variants, which is significantly lower than reported earlier. Interestingly, the increased viral load for the Delta variant seemed to be age-dependent, regardless of sex, as the viral load was about 14-fold higher for Delta compared to the non-VOC or Alpha variant in age group 0–20 years and fourfold higher in age group 21–40 years, while there was no difference in viral load between variants in age groups 41–60 and 61+ years, most likely as a consequence of a higher degree of vaccination in the older age groups.

Background Neisseria gonorrhoeae (NG) is a common bacterial sexually transmitted infection (STI). Currently, there are limited data on the bacterial load in both men and women, and on both genital and extra-genital sites. Therefore, we quantified NG bacterial load in a large population of women, heterosexual men, and men who have sex with men (MSM) at three different anatomical sites. Methods NG-positive samples (n=1265) of STI clinic consultations (n=944) were tested for NG with the Roche Cobas® 4800 system and Cq-values were used as an inversely proportional measure for NG bacterial load after interpolation from a standard curve. Bacterial load was compared between sample material and sex using t-tests. Results The following mean NG loads were observed: urine, 4.5 ±1.0 log10 CFU/mL; vaginal swabs, 4.3 ±1.1 log10 CFU/mL; anorectal swabs (women), 4.0 ±1.2 log10 CFU/mL; anorectal swabs (men), 4.5 ±1.3 log10 CFU/mL; oropharyngeal swabs (women), 2.8 ±0.9 log10 CFU/mL; and oropharyngeal swabs (men), 3.2 ±1.0 log10 CFU/mL. Oropharyngeal swabs had a significantly lower NG load (p<0.001) compared to genital and anorectal samples. Load did not differ between men and women. Conclusions This is the first study that determined NG load in both women and men at three anatomical sites. The substantial NG load at all sample sites suggest that all sites may have transmission potential. However, the oropharyngeal site presents the lowest bacterial load. Men and women have a similar NG load on separate anatomical sites arguing for similar transmission potential and similar clinical relevance.