H因子结合蛋白的非功能变异体作为脑膜炎球菌的候选疫苗

脑膜炎奈瑟菌是人类专属病原体，是脑膜炎和败血症的主要病因。 H因子结合蛋白（ fHbp ）是一种毒力因子，它通过高亲和性地结合人的补体调节因子H（ fH）保护脑膜炎奈瑟菌不受天然免疫力的伤害，同时也是正在研发中的预防脑膜炎球菌病疫苗中的关键抗原。 fHbp可分为3个不同的群（ V1、V2和V3），都能诱导有限的免疫交叉反应性。 fH与fHbp的相互作用能损害这种抗原的免疫原性，因为这阻碍了向fHbp中的抗原表位的接近，这为研究非功能性fHbp作为疫苗候选物提供了依据。这里作者鉴定了两个非功能性V3 fHbps fHbp T286A和fH-bpE313A ，各自含有一个单氨基酸替代从而导致与fH亲和性的显著减弱而又不影响该蛋白的折叠。非功能性fHbps的免疫原性用表达单一嵌合性fH （其上含有人fH中涉及与fHbp相结合的区域）的转基因小鼠进行评估。野生型V3 fHbp、V3 fHbpT286A 和V3 fHbpE313A 所诱导的抗V3 fHbp 的抗体滴度没有差异，说明非功能性fHbp保留了它们的免疫原性。

Global Transmission of the penA Allele 60.001–Containing High-Level Ceftriaxone-Resistant Gonococcal FC428 Clone and Antimicrobial Therapy of Associated Cases:A Review

Neisseria gonorrhoeae is a multidrug-resistant bacterial pathogen for which ceftriaxone is the only remaining recommended first-line therapy.However,ceftriaxone susceptibility has been waning in a number of countries over the last decade and ceftriaxone treatment failures have been reported,commonly as a result of sporadic high-level ceftriaxone-resistant strains.In recent years,N.gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or strains that acquired its main ceftriaxone resistance determinant,penA allele 60.001,have shown global transmission,resulting in ceftriaxone treatment failure in a number of cases.The FC428 clone was first encountered in Japan in 2015 and subsequently in China,Europe,Australia,North America and Southeast Asia afterward.Strains associated with the FC428 clone commonly display a ceftriaxone minimum inhibitory concentration of 0.5-1 mg/L.However,where penA alleles encountered in sporadic high-level ceftriaxone-resistant isolates induce an in vitro growth defect,penA allele 60.001 does not seem to affect in vitro growth.The limited impact of penA allele 60.001 on biological fitness might be associated with its successful global transmission.Although the FC428 clone displays high-level ceftriaxone resistance,most gonorrhea cases associatedwith this clone were still successfully curedwith ceftriaxonewhen intramuscular or intravenous doses of 500mg to 2 g were used.A successful alternative therapy seems to be ertapenem given at 1-g doses,although further clinical studies are required to validate ertapenemefficacy.This review summarizes the global transmission of strains associated with the FC428 clone and antimicrobial treatment of associated cases.

Infectious Microbes&Diseases Contributing to COVID-19 Prevention and Control

Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed infections and 6,709,387 confirmed deaths as of January 19,2023.1 Facing this remarkably fast developing pandemic with limited knowledge on many aspects of the disease,including transmission,effective infection control,morbidity and treatment,researchers and practitioners worldwide have switched their focus to COVID-19–related research and practices.According to incomplete statistics,more than 330,000 COVID-19–related publications have been indexed in PubMed by January 19,2023,2 which carried out comprehensive and multifaceted studies on COVID-19.These research findings have played a key role in controlling the spread of COVID-19,treating severe and/or critical cases,and reducing the morbidity and mortality.

Introducing Our New Journal: Infectious Microbes & Diseases

The 20th century has witnessed a steep decline of the global burden of infectious diseases due to improved hygiene conditions in large parts of the world and the introduction of vaccines and antimicrobials.However,in today’s global landscape infectious diseases still remain a major concern.According to the 2017 Global Burden of Disease Study,communicable diseases still accounted for approximately 8.14 million deaths,which was 14.6%of all age deaths for that year.1 Furthermore,it accounted for 24%of all age years of life lost.Infectious disease outbreaks have been rising since the 1980s2 and pathogenic microbes are now spreading faster geographically due to international traveling.Simultaneously,emerging and reemerging infectious diseases are being identified faster than ever before.The resurgence of these emerging and re-emerging diseases might be caused by climate change,changing international food chains,and a rise in antimicrobial resistance.According to a recent report on antimicrobial resistance issued by the UK government,3 unless proper action is taken,drugresistant diseases might cause 10 million deaths per year by 2050,costing the global economy up to 100 trillion dollar.

Determination of Fusidic Acid Susceptibility of Multidrug-resistant Gonococcal Isolates from China

The currently recommended gonococcal therapies are rapidly losing efficacy and;therefore,novel options for treatment are urgently required to ensure future treatment remains available.Here we investigated the susceptibility of 379 contemporary clinical Neisseria gonorrhoeae isolates from China for susceptibility to fusidic acid.These isolates include numerous multidrug-resistant strains with resistance or reduced susceptibility against ceftriaxone and/or azithromycin,antimicrobials that are currently recommended as a first-line dual therapy.Although official susceptibility breakpoints have not been established,all gonococcal isolates appeared to be susceptible to fusidic acid,with the majority of isolates displaying a minimal inhibitory concentration(MIC)of 0.25 or 0.5mg/L.Overall,the MIC90 was 0.5mg/L,with a MIC range of 0.08-2mg/L.Importantly,no correlation between fusidic acid susceptibility and susceptibility to ceftriaxone or azithromycin was observed.Further analysis of gonococcal survival curves indicated that fusidic acid was only mildly bactericidal at the highest tested concentrations(4
MIC).In conclusion,fusidic acid displayed consistent antimicrobial activity against N.gonorrhoeae and,given the absence of cross-resistance with ceftriaxone and azithromycin,might be interesting for further evaluation of single or dual antimicrobial therapies in combination with ceftriaxone or azithromycin.

Introducing the New Versions of Chinese Diagnosis and Treatment Protocol for COVID-19

Since the first outbreak of COVID-19 in January 2020,the pandemic has lasted already for 2½years,causing 564,126,546 confirmed infections and 6,371,354 confirmed deaths worldwide by July 22,2022.1 In addition to the large number of deaths caused by the disease,the COVID-19 pandemic has also had a huge impact on the world economy.Not only have the transportation,tourism,catering,cultural and entertainment industries,and other personnel-intensive industries been directly impacted,but also a large number of people have been isolated and controlled or accepted home office work,which in turn affected all walks of life.

Role of Outer Membrane Vesicles in Bacterial Physiology and Host Cell Interactions

Outer membrane vesicles(OMVs)are spherical particles shed from the outer membrane of Gram-negative bacteria,which contain the typical components present in the outer membrane,although enrichment of specific molecules may occur,and furthermore a variety of periplasmic components and occasionally some inner membrane or cytoplasmic fractions.Although the detailed mechanisms of OMV biogenesis are not fully illuminated yet,several models have been proposed that demonstrate OMV biogenesis is an orchestrated well-regulated process.OMV secretion offers a way for both intra-and inter-species bacterial communication and for interaction or modulation of the bacterial environment.Therefore,OMVs have proven to be functionally versatile and important for bacterial physiology and survival of the host environment.In the host,OMVs are internalized via host cell endocytosis pathways,allowing them to subsequently trigger a variety of cellular responses.In this review,we discuss the recent advances in establishing the mechanisms involved in OMV biogenesis and the impact of OMVs on bacterial physiology and intracellular modulation of the host.

Antibiotic Resistance and Treatment Options for Multidrug-Resistant Gonorrhea

Gonorrhea is a sexually transmitted disease with a high global incidence.Its causative agent,Neisseria gonorrhoeae,has shown a remarkable flexibility to adapt and become resistant to all antimicrobials introduced over the past century for gonococcal therapy.The currently last available first-line therapy that is recommended in most countries is ceftriaxone.However,resistance levels against ceftriaxone are rising globally and incidences of confirmed treatment failure are increasingly encountered,particularly with the global spreading of the ceftriaxone-resistant FC428 clone in recent years.Resistance against most antimicrobials has been the result of adaptive genomic mutations that reduce affinity of the antimicrobial to its target protein or rRNA,although most multidrug-resistant strains also appear to have an upregulated multidrug efflux pump.To ensure gonococcal treatment remains available in the future,alternative therapies are urgently needed.Therefore,both alternative clinically approved antimicrobials and novel antimicrobials have been intensely studied both in gonococcal susceptibility analyses and clinical efficacy trials.Although there have been some limited successes,all studied alternative therapies that reached clinical trials have displayed some shortcomings in their efficacy against pharyngeal infections and/or overlapping resistance determinants with previously or currently used antimicrobials.This review summarizes the development of gonococcal antimicrobial resistance over the past century,describes the mechanisms involved in antimicrobial resistance,and provides an overview of the alternative therapies that have been under investigation this past decade.