Objective To describe prominent authorship positions held by women and the overall percentage of women co-authoring manuscripts submitted during the covid-19 pandemic compared with the previous two years. Design Cross sectional study. Setting Nine specialist and two large general medical journals. Population Authors of research manuscripts submitted between 1 January 2018 and 31 May 2021. Main outcome measures Primary outcome: first author’s gender. Secondary outcomes: last and corresponding authors’ gender; number (percentage) of women on authorship byline in “pre-pandemic” period (1 January 2018 to 31 December 2019) and in “covid-19” and “non-covid-19” manuscripts during pandemic. Results A total of 63 259 manuscripts were included. The number of female first, last, and corresponding authors respectively were 1313 (37.1%), 996 (27.9%), and 1119 (31.1%) for covid-19 manuscripts (lowest values in Jan-May 2020: 230 (29.4%), 165 (21.1%), and 185 (22.9%)), compared with 8583 (44.9%), 6118 (31.2%), and 7273 (37.3%) for pandemic non-covid-19 manuscripts and 12 724 (46.0%), 8923 (31.4%), and 10 981 (38.9%) for pre-pandemic manuscripts. The adjusted odds ratio of having a female first author in covid-19 manuscripts was <1.00 in all groups (P<0.001) compared with pre-pandemic (lowest in Jan-May 2020: 0.55, 98.75% confidence interval 0.43 to 0.70). The adjusted odds ratio of having a woman as last or corresponding author was significantly lower for covid-19 manuscripts in all time periods (except for the two most recent periods for last author) compared with pre-pandemic (lowest values in Jan-May 2020: 0.74 (0.57 to 0.97) for last and 0.61 (0.49 to 0.77) for corresponding author). The odds ratios for pandemic non-covid-19 manuscripts were not significantly different compared with pre-pandemic manuscripts. The median percentage of female authors on the byline was lower for covid-19 manuscripts (28.6% in Jan-May 2020) compared with pre-pandemic (36.4%) and non-covid-19 pandemic manuscripts (33.3% in Jan-May 2020). Gender disparities in all prominent authorship positions and the proportion of women authors on the byline narrowed in the most recent period (Feb-May 2021) compared with the early pandemic period (Jan-May 2020) and were very similar to values observed for pre-pandemic manuscripts. Conclusions Women have been underrepresented as co-authors and in prominent authorship positions in covid-19 research, and this gender disparity needs to be corrected by those involved in academic promotion and awarding of research grants. Women attained some prominent authorship positions equally or more frequently than before the pandemic on non-covid-19 related manuscripts submitted at some time points during the pandemic.
Burkholderia pseudomallei is the causative agent of melioidosis, a serious disease endemic in Southeast Asia and Northern Australia. Antibiotic treatment is lengthy and relapse often occurs. Finafloxacin is a novel fluoroquinolone with increased antibacterial activity in acidic conditions in contrast to other fluoroquinolones which demonstrate reduced activity at a lower pH. Therefore, finafloxacin may have improved efficacy against B. pseudomallei, which can survive within host cells where the local pH is acidic. In vitro analysis was performed using MICs, minimal bactericidal concentrations (MBCs), time-kill assays, persister cell assays, and macrophage assays. Finafloxacin showed increased bactericidal activity at pH 5 in comparison to pH 7 and ciprofloxacin at pH 5. In vivo studies in BALB/c mice included pharmacokinetic studies to inform an appropriate dosing regimen. Finafloxacin efficacy was evaluated in an inhalational murine model of melioidosis where antibiotic treatment was initiated at 6 or 24 h postchallenge and continued for 14 days, and mice were observed for 63 days. The survival of infected mice following 14 days of treatment was 80%, 60% or 0% for treatments initiated at 6 h and 60%, 30% or 0% for treatments initiated at 24 h for finafloxacin, co-trimoxazole, or ciprofloxacin, respectively. In summary, finafloxacin has increased bactericidal activity for B. pseudomallei under acidic conditions in vitro and improves survival in a murine model of melioidosis compared with those for ciprofloxacin. Furthermore, finafloxacin improves bacteriological clearance compared with that of co-trimoxazole, suggesting it may offer an effective postexposure prophylaxis against B. pseudomallei.
Burkholderia pseudomallei is the causative agent of the tropical disease melioidosis. Its genome encodes an arsenal of virulence factors that allow it, when required, to switch from a soil dwelling bacterium to a deadly intracellular pathogen. With a high intrinsic resistance to antibiotics and the ability to overcome challenges from the host immune system, there is an increasing requirement for new antibiotics and a greater understanding into the molecular mechanisms of B . pseudomallei virulence and dormancy. The peptidoglycan remodeling enzymes, lytic transglycosylases (Ltgs) are potential targets for such new antibiotics. Ltgs cleave the glycosidic bonds within bacterial peptidoglycan allowing for the insertion of peptidoglycan precursors during cell growth and division, and cell membrane spanning structures such as flagella and secretion systems. Using bioinformatic analysis we have identified 8 putative Ltgs in B . pseudomallei K96243. We aimed to investigate one of these Ltgs, LtgG (BPSL3046) through the generation of deletion mutants and biochemical analysis. We have shown that LtgG is a key contributor to cellular morphology, division, motility and virulence in BALB/c mice. We have determined the crystal structure of LtgG and have identified various amino acids likely to be important in peptidoglycan binding and catalytic activity. Recombinant protein assays and complementation studies using LtgG containing a site directed mutation in aspartate 343, confirmed the essentiality of this amino acid in the function of LtgG.
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