Latest Publications
Macrolide-resistant Mycoplasma pneumoniae resurgence in Chinese children in 2023: a longitudinal, cross-sectional, genomic epidemiology study
Chao Yan,Shanwei Tong, Yarong Wu, Yujie Chen,Xinyu Jia,Yan Guo,Mengnan Cui,Guangqian Pei, Zuming Zhang, Hao Zhou, BAdmin , Kai Mu,Xue Ren,Bing Du, Hanqing Zhao,Yanling Feng,Jinghua Cui,Yuyan Xia, MBBS , Zhen Wang, Yu Sun,Prof Linqing Zhao, Prof Chuangli Hao, Zhijie Zhu, Shengqiang Luo, Han Zhang, Yongjun Wang , Prof Lili Zhong, DehuiChen , Prof Yong Yin , Longji Hu, Prof Yuehua Ke, Prof Guanhua Xue, Prof Ling Cao, , Prof Xavier Didelot, Prof Jing Yuan, Prof Yujun Cui,
Background: After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen.
Methods: We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013–22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen’s evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China.
Findings: Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China’s large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China.
Interpretation: Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen.
Predictors of success for human assisted reproduction
Amelia Longa, Daniel N. Franklin
As global fertility rates decline, improving the success rates of assisted reproductive technologies (ART) becomes ever more important. Many factors impact the success of ART and understanding these is key to enhancing treatment efficacy. We analysed a large UK national dataset from the Human Fertilisation and Embryology Authority to determine which factors predict success of ART. Binary logistic regression identified significant predictors of biochemical pregnancy. Patient age, diagnosed ovulatory disorder, specific ART treatment, PGT-A testing, donor egg, number of embryos transferred, patient ethnicity, and day of embryo transfer were significant predictors of success. These results add detail and evidence to previous studies and the insights can inform clinical practices to enhance ART success rates.
Engineered bacteriophages for therapeutic and diagnostic applications
Kandas Traore, Damien Seyer, Agnes Mihajlovski, Antonia P Sagona
Antimicrobial resistance represents one of the most serious threats to both public health and economic sustainability. One of the promising approaches to address this problem is phage therapy – treatment of pathogenic bacterial infections using bacteriophages. Bacteriophages have a narrow host spectrum of activity, minimal side effects and self-replication at the infection site, which positions them as promising candidates to complement or replace conventional antibiotics. Moreover, they can be easily genetically modified to enhance their effectiveness and safety. In this At a Glance article, we highlight the timely relevance of engineered phages as an innovative solution in a rapidly evolving healthcare landscape. First, we introduce bacteriophages' life cycle, ecology and therapeutic history, emphasizing their role in One Health strategies. Then, we describe advanced engineering techniques that can be used to expand bacteriophages' functionalities. Finally, we discuss innovative applications of engineered bacteriophages in biotechnological applications and as a potential countermeasure for antimicrobial resistance, including serving as a shuttle for delivering genes and drugs to the targeted bacterial and eukaryotic cells, targeting intracellular bacteria, contributing to vaccine development, facilitating advancements in tissue engineering and improving bacteriophages' antibacterial properties.
Developmental fates and N2-fixing efficiency of terminally-differentiated versus undifferentiated bacteroids from legume nodules
Carmen Sánchez-Cañizares , Raphael Ledermann , Joseph McKenna, Thomas J Underwood , Marcela Mendoza-Suárez , Rob Green , Karunakaran Ramakrishnan , Alison K East , Isabel Webb , Charlotte Kirchhelle , Beatriz Jorrín , Gerhard Saalbach , Euan K James , Flavia Moreira-Leite , Jason Terpolilli , Philip S Poole
Within legume root nodules, rhizobia differentiate into bacteroids, which reduce N2 into NH3 for secretion to the plant. Bacteroids may be swollen and terminally differentiated or non-swollen and can regenerate outside nodules. It is unclear why these different endosymbiotic lifestyles exist and whether they differ in symbiotic efficiency. Here, we compared N2 fixing bacteroids of the near isogenic strains Rhizobium leguminosarum bv. phaseoli 4292 (Rlp4292) and R. leguminosarum bv. viciae A34 (RlvA34), nodulating Phaseolus vulgaris (common bean) and Pisum sativum (pea), respectively. The larger bean plants fixed more N2, but peas fixed 1.6-3-fold more per unit nodule mass. Values per unit volume were similar between bean and pea because bean nodules are 2.7-fold denser (i.e., mass per unit volume). Bean nodules have higher numbers of smaller (∼1/5 the volume) bacteroids than peas. Bean bacteroids are denser (i.e., 2.5-fold protein per unit volume) although less closely packed than pea bacteroids (i.e. more space between bean bacteroids). Critically, pea bacteroids, fix N2 at higher rates versus bean per unit bacteroid protein, as protein expression is skewed towards N2 fixation and TCA-cycle enzymes. Pea bacteroids infect 1.6 times the percentage of nodule volume of beans (i.e., 14.2% versus 9.1%). Overall, the increased packing density of pea bacteroids, as well as the bias of their proteome to nitrogenase, associated N2 fixation processes, and dicarboxylate metabolism, contributes to their greater symbiotic efficiency, which is likely driven by plant antimicrobial peptides.
Unlocking plant health survey data: An approach to quantify the sensitivity and specificity of visual inspections
Matt Combes, Nathan Brown, Robin N. Thompson, Alexander Mastin, Peter Crow, Stephen Parnell
Invasive plant pests and pathogens cause substantial environmental and economic damage. Visual inspection remains a central tenet of plant health surveys, but its sensitivity (probability of correctly identifying the presence of a pest) and specificity (probability of correctly identifying the absence of a pest) are not routinely quantified. As knowing sensitivity and specificity of visual inspection is critical for effective contingency planning and outbreak management, we address this deficiency using empirical data and statistical analyses. Twenty-three citizen scientist surveyors assessed up to 175 labelled oak trees for three symptoms of acute oak decline. The same trees were also assessed by an expert who has monitored these individual trees annually for over a decade. The sensitivity and specificity of surveyors was calculated using the expert data as the ‘gold-standard’ (i.e., assuming perfect sensitivity and specificity). The utility of an approach using Bayesian modelling to estimate the sensitivity and specificity of visual inspection in the absence of a rarely available ‘gold-standard’ dataset was then examined with simulated plant health survey datasets. There was large variation in sensitivity and specificity between surveyors and between different symptoms, although the sensitivity of detecting a symptom was positively related to the frequency of the symptom on a tree. By leveraging surveyor observations of two symptoms from a minimum of 80 trees on two sites, with reliable prior knowledge of sites with a higher (~0.6) and lower (~0.3) true disease prevalence we show that sensitivity and specificity can be estimated without ‘gold-standard’ data using Bayesian modelling. We highlight that sensitivity and specificity will depend on the symptoms of a pest or disease, the individual surveyor, and the survey protocol. This has consequences for how surveys are designed to detect and monitor outbreaks, as well as the interpretation of survey data that is used to inform outbreak management.
Updated Priorities for Cerebroprotection Trials
Sean Savitz, Edgar Samaniego, David Liebeskind, Johannes Boltze
A STAIR XIII workshop was held to discuss aspects of trials likely to have the greatest impact on detecting meaningful treatment effects of cerebroprotection in acute stroke. Intended goals for hyperacute protection should be focused on preserving penumbral tissue and delaying infarct core growth to augment the impact of reperfusion therapies. Infarct volume is a biologically and clinically meaningful surrogate imaging marker to assess the treatment effects of cerebroprotection. Lastly, clinical outcome measures for cerebroprotection should include domain-specific and patient-centered outcomes to detect clinically meaningful changes across multiple functional domains.