Since its discovery in the 19th century, the complement system has developed into a clinically significant entity. The complement system has been implicated in a variety of clinical conditions, from autoimmune diseases to ischemia-reperfusion injury in transplantation. This article charts the historical progress of our understanding of the complement system and provides a synopsis on the activation pathways and its inherent regulators.

MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, competitive ability and significant degradation in cell membrane and cytoplasmic structures, compared to expression of catalytically inactive MCR-1 (E246A) or MCR-1 soluble component. Lipopolysaccharide (LPS) extracted from mcr-1 strains induces lower production of IL-6 and TNF, when compared to control LPS. Compared to their parent strains, high-level colistin resistance mutants (HLCRMs) show reduced fitness (relative fitness is 0.41–0.78) and highly attenuated virulence in a Galleria mellonella infection model. Furthermore, HLCRMs are more susceptible to most antibiotics than their respective parent strains. Our results show that the bacterium is challenged to find a delicate equilibrium between expression of MCR-1-mediated colistin resistance and minimalizing toxicity and thus ensuring cell survival.

Previous meta-analyses have reported a significant association between pulmonary colonization with Ureaplasma and development of bronchopulmonary dysplasia (BPD). However, because few studies reporting oxygen dependency at 36 weeks corrected gestation were previously available, we updated the systematic review and meta-analyses to evaluate the association between presence of pulmonary Ureaplasma and development of BPD. Five databases were searched for articles reporting the incidence of BPD at 36 weeks postmenstrual age (BPD36) and/or BPD at 28 days of life (BPD28) in Ureaplasma colonized and noncolonized groups. Pooled estimates were produced using random effects meta-analysis. Meta-regression was used to assess the influence of difference in gestational age between the Ureaplasma-positive and Ureaplasma-negative groups. The effects of potential sources of heterogeneity were also investigated. Of 39 studies included, 8 reported BPD36, 22 reported BPD28 and 9 reported both. The quality of studies was assessed as moderate to good. There was a significant association between Ureaplasma and development of BPD36 (odds ratio = 2.22; 95% confidence intervals: 1.42-3.47) and BPD28 (odds ratio = 3.04; 95% confidence intervals: 2.41-3.83). Sample size influenced the odds ratio, but no significant association was noted between BPD28 rates and difference in gestational age between Ureaplasma colonized and noncolonized infants (P = 0.96). Pulmonary colonization with Ureaplasma continues to be significantly associated with development of BPD in preterm infants at both 36 weeks postmenstrual age and at 28 days of life. This association at BPD28 persists regardless of difference in gestational age.

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein_269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A^∗02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as “variants of concern,” was not recognized by the large CD8 T cell response seen across cohorts of HLA A^∗02⁺ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Background: Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia, with large epidemics previously described to occur every 4 to 7 years. Aim: To better understand the diagnostic methods used to detect M. pneumoniae; to better understand M. pneumoniae testing and surveillance in use; to identify epidemics; to determine detection number per age group, age demographics for positive detections, concurrence of epidemics and annual peaks across geographical areas; and to determine the effect of geographical location on the timing of epidemics. Methods: A questionnaire was sent in May 2016 to Mycoplasma experts with national or regional responsibility within the ESCMID Study Group for Mycoplasma and Chlamydia Infections in 17 countries across Europe and Israel, retrospectively requesting details on M. pneumoniae-positive samples from January 2011 to April 2016. The Moving Epidemic Method was used to determine epidemic periods and effect of country latitude across the countries for the five periods under investigation. Results: Representatives from 12 countries provided data on M. pneumoniae infections, accounting for 95,666 positive samples. Two laboratories initiated routine macrolide resistance testing since 2013. Between 2011 and 2016, three epidemics were identified: 2011/12, 2014/15 and 2015/16. The distribution of patient ages for M. pneumoniae-positive samples showed three patterns. During epidemic years, an association between country latitude and calendar week when epidemic periods began was noted. Conclusions: An association between epidemics and latitude was observed. Differences were noted in the age distribution of positive cases and detection methods used and practice. A lack of macrolide resistance monitoring was noted.