FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 是一本领先的专业期刊，发表了经过严格同行评审的所有病原微生物及其与宿主相互作用的研究。路易斯维尔大学的主编 YOUSEF ABU KWAIK 得到了杰出的国际专家编辑委员会的支持。这本多学科开放获取期刊处于向全球研究人员、学者、临床医生和公众传播和交流科学知识和有影响力的发现的最前沿。细胞和感染微生物学前沿包括对细菌、真菌、寄生虫、病毒、内共生菌、朊病毒的研究以及所有微生物病原体以及微生物群及其对各种宿主健康和疾病的影响。研究方法包括分子微生物学、细胞微生物学、基因调控、蛋白质组学、信号转导、致病进化、基因组学、结构生物学、毒力因子以及模型宿主。对抗宿主感染因子的研究领域包括宿主先天性和适应性免疫反应以及对各种病原微生物的代谢限制，针对各种病原微生物的疫苗设计和开发，以及抗生素耐药机制及其应对措施。

Frontiers in Cellular and Infection Microbiology is a leading professional journal that publishes rigorously peer-reviewed research on all pathogenic microorganisms and their interactions with hosts. The journal is led by Editor-in-Chief Yousef Abu KwaiK from the University of Louisville, supported by an outstanding international editorial board of experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, scholars, clinicians, and the public worldwide. The journal covers research on bacteria, fungi, parasites, viruses, endosymbionts, and prions, as well as the effects of these microbial pathogens and their microbiomes on host health and disease. Research methods include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, virulence factors, and model hosts. Research areas targeting host infection factors include innate and adaptive immune responses, metabolic restrictions against various pathogens, vaccine design and development, and antibiotic resistance mechanisms and their countermeasures.

《Frontiers in Cellular and Infection Microbiology》是一本领先的专业期刊，发表经过严格同行评审的所有病原微生物及其与宿主相互作用的研究。该期刊由路易斯维尔大学的主编Yousef Abu KwaiK领导，并得到了杰出的国际专家编辑委员会的支持。这本多学科的开放获取期刊致力于向全球研究人员、学者、临床医生和公众传播科学知识和重要发现。期刊涵盖细菌、真菌、寄生虫、病毒、内共生菌和朊病毒等微生物的研究，以及这些微生物病原体及其微生物群对宿主健康和疾病的影响。研究方法包括分子微生物学、细胞微生物学、基因调控、蛋白质组学、信号转导、致病进化、基因组学、结构生物学、毒力因子以及模型宿主。针对宿主感染因子的研究领域包括宿主的先天性和适应性免疫反应、对各种病原微生物的代谢限制、疫苗设计和开发，以及抗生素耐药机制及其应对措施。

Frontiers in Cellular and Infection Microbiology

Several strains of lactic acid bacteria are potent probiotics and can cure a variety of diseases using different modes of actions. These bacteria produce antimicrobial peptides, bacteriocins, which inhibit or kill generally closely related bacterial strains and other pathogenic bacteria such as Listeria, Clostridium, and Salmonella. Bacteriocins are cationic peptides that kill the target cells by pore formation and the dissipation of cytosolic contents, leading to cell death. Bacteriocins are also known to modulate native microbiota and host immunity, affecting several health-promoting functions of the host. In this review, we have discussed the ability of bacteriocin-producing probiotic lactic acid bacteria in the modulation of gut microbiota correcting dysbiosis and treatment/maintenance of a few important human disorders such as chronic infections, inflammatory bowel diseases, obesity, and cancer.

None Anjana

Santosh Kumar Tiwari

Front. Cell. Infect. Microbiol.

Bacteriocin-Producing Probiotic Lactic Acid Bacteria in Controlling Dysbiosis of the Gut Microbiota

In this report, we describe the first case of infective endocarditis caused by Mycobacterium kansasii in a 45-year-old male patient who presented with a 10-day fever and decompensated cirrhosis. Despite negative results in blood culture and pathology, we employed metagenomic next-generation sequencing (mNGS) to analyze the genome sequences of both the host and microbe. The copy number variation (CNV) indicated a high risk of liver disease in the patient, which correlated with biochemical examination findings. Notably, M. kansasii sequences were detected in peripheral blood samples and confirmed through Sanger sequencing. Unfortunately, the patient's condition deteriorated, leading to his demise prior to heart surgery. Nevertheless, we propose that mNGS could be a novel approach for diagnosing M. kansasii infection, particularly in cases where blood culture and pathology results are unavailable. It is important to consider M. kansasii infection as a potential cause of endocarditis and initiate appropriate anti-infection treatment.

Liuqing Yang

Ling Peng

Ke Yuan

Kanru Cai

Cheng Feng

Gendong Yang

Shunyao Wang

Xiuyun Zhu

Jieyun Zhang

Fuxiang Wang

Hongzhou Lu

Case Report: Mycobacterium kansasii causing infective endocarditis explored by metagenomic next-generation sequencing

Metagenomic next-generation sequencing (mNGS) technology is helpful for the early diagnosis of infective endocarditis, especially culture-negative infective endocarditis, which may guide clinical treatment. The purpose of this study was to compare the presence of culture-negative infective endocarditis pathogens versus culture-positive ones, and whether mNGS test results could influence treatment regimens for patients with routine culture-negative infective endocarditis.The present study enrolled patients diagnosed with infective endocarditis and tested for mNGS in the First Affiliated Hospital of Zhengzhou University from February 2019 to February 2022 continuously. According to the culture results, patients were divided into culture-negative group (Group CN, n=18) and culture-positive group (Group CP, n=32). The baseline characteristics, clinical data, pathogens, 30 day mortality and treatment regimen of 50 patients with infective endocarditis were recorded and analyzed.Except for higher levels of PCT in the Group CN [0.33 (0.16-2.74) ng/ml vs. 0.23 (0.12-0.49) ng/ml, P=0.042], there were no significant differences in the basic clinical data and laboratory examinations between the two groups (all P>0.05). The aortic valve and mitral valve were the most involved valves in patients with infective endocarditis (aortic valve involved: Group CN 10, Group CP 16; mitral valve involved: Group CN 8, Group CP 21; P>0.05) while 9 patients had multiple valves involved (Group CN 2, Group CP 7; P>0.05). The detection rate of non-streptococci infections in the Group CN was significantly higher than that in the Group CP (9/18 vs. 3/32, P=0.004). There was no significant difference in patients with heart failure hospitalization and all-cause death at 30 days after discharge (3 in Group CN vs. 4 in Group CP, P>0.05). It is worth noting that 10 patients with culture-negative infective endocarditis had their antibiotic regimen optimized after the blood mNGS.Culture-negative infective endocarditis should be tested for mNGS for early diagnosis and to guide clinical antibiotic regimen.

Shao-Lin Li

Xi Zhao

Jun-Zhong Tao

Zhen-Zhen Yue

Xiao-Yan Zhao

Application of metagenomic next-generation sequencing in patients with infective endocarditis

B rucellosis is a common zoonotic disease that is widely spread worldwide and poses a major threat to human health. Clinically, it often presents with non-specific symptoms such as fever, excessive sweating, malaise, myalgia, arthralgia, loss of appetite, weight loss, and enlarged liver, spleen and lymph nodes. The disease has a long and recurrent course, often accumulating in multiple systems and organs. Of these, osteoarticular involvement is the most common complication, with a prevalence of approximately 2-77%, usually manifesting as spondylitis, sacroiliac arthritis and peripheral arthritis. Hepatosplenomegaly is seen in about 50% of patients with b rucellosis, and gastrointestinal disturbances such as abdominal pain, nausea, and vomiting are common. Although respiratory involvement is less common, pneumonia, pleurisy, pleural effusion, and pulmonary nodules have been reported. Besides, approximately 2-20% of cases involve infections of the male genitourinary system, mainly manifesting as unilateral epididymal-orchitis and orchitis. The most serious complication facing b rucellosis is cardiovascular involvement, and although the overall mortality rate of b rucellosis is about 1% and the incidence of b rucellosis endocarditis is less than 2%, more than 80% of deaths are associated with endocarditis. Furthermore, b rucellosis is complicated by hematologic disease, with anemia occurring in approximately 20-53% of children during the acute phase. In addition, the neurological incidence of b rucellosis is about 0.5-25%, mainly manifested as meningitis. In this study, we review the multisystem complications of brucellosis with the aim of improving early diagnosis, timely treatment and prevention of long-term complications.

Min Jin

Zixu Fan

Ruifang Gao

Xingnan Li

Zhixiang Gao

Zhanli Wang

Research progress on complications of Brucellosis

布鲁氏菌病并发症研究进展

Background The objective of this study is to utilize metagenomic next-generation sequencing (mNGS) to analyze the risk factors causing negative microbial cultures, comprehensively delineate the microbial profiles neglected by traditional cultures, and optimize the pathogenetic diagnostic procedure accordingly. Research design and methods We enrolled 341 patients diagnosed with OI at our center between 2016 and 2022, and gathered data including age, gender, clinical diagnosis, duration of antibiotic use prior to sampling, microbial culture results, and mNGS results for these patients. According to microbial detection results, risk factors for negative microbial culture and mNGS results were investigated through univariate and multivariate analyses, and the microbial profile in cases with negative microbial cultures was summarized in conjunction with mNGS results. Building upon this, we suggest strategies to enhance the positivity rate of microbial cultures based on clinical experience. Results Invasive osteoarticular infection (IOI), multi-infections, rare pathogen infections, and prior antibiotic use are risk factors for negative microbial cultures. When the duration of prior antibiotic use is ≥3 days, mNGS demonstrates significantly higher pathogen detection efficiency than microbial culture. Moreover, the risk of negative microbial culture increases by 4.8 times with the exposure to each additional risk factor (OR=4.043, 95%CI [2.835, 5.765], P &amp;lt;0.001). Additionally, over one-third of culture-negative OI involve polymicrobial infections or rare pathogens. Conclusions Clinicians should tailor microbial culture strategies based on patient conditions. When needed, they can collaborate with mNGS or optimize microbial culture conditions based on mNGS results to enhance the efficiency of pathogen diagnosis.

Haiqi Ding

Jiexin Huang

Lan Lin

Yang Chen

Qijin Wang

Wenbo Li

Ying Huang

Xinyu Fang

Wenming Zhang

Shedding light on negative cultures in osteoarticular infections: leveraging mNGS to unravel risk factors and microbial profiles

In recent years, the emergence and widespread dissemination of the coronavirus SARS-CoV-2 has posed a significant threat to global public health and social development. In order to safely and effectively prevent and control the spread of coronavirus diseases, a profound understanding of virus-host interactions is paramount. Cellular autophagy, a process that safeguards cells by maintaining cellular homeostasis under diverse stress conditions. Xenophagy, specifically, can selectively degrade intracellular pathogens, such as bacteria, fungi, viruses, and parasites, thus establishing a robust defense mechanism against such intruders. Coronaviruses have the ability to induce autophagy, and they manipulate this pathway to ensure their efficient replication. While progress has been made in elucidating the intricate relationship between coronaviruses and autophagy, a comprehensive summary of how autophagy either benefits or hinders viral replication remains elusive. In this review, we delve into the mechanisms that govern how different coronaviruses regulate autophagy. We also provide an in-depth analysis of virus-host interactions, particularly focusing on the latest data pertaining to SARS-CoV-2. Our aim is to lay a theoretical foundation for the development of novel coronavirus vaccines and the screening of potential drug targets.

Jiarong Yu

Shengqiang Ge

Jinming Li

Yongqiang Zhang

Jiao Xu

Yingli Wang

Shan Liu

Xiaojing Yu

Zhiliang Wang

Interaction between coronaviruses and the autophagic response

冠状病毒与自噬反应之间的相互作用

Background Azvudine (AZV), the first Chinese oral anti-coronavirus disease 2019 (COVID-19) drug, has shown substantial clinical benefits to viral clearance and prognosis in patients with mild and common COVID-19. However, there is no evidence in severe hospitalized COVID-19 patients. Methods In this multicenter study, we analyzed 209 severe hospitalized COVID-19 patients in four hospitals. All the clinical data and the 28-day composite outcomes were recorded. All of the patients were categorized into two groups according to drug: the dexamethasone (DXM) group and the azvudine plus dexamethasone (AZV+DXM) group. Results There were no differences in sex, age, BMI, and underlying diseases between the two groups. The ratio of the 28-day composite outcome was lower for the AZV+DXM group than that for the DXM group (16.97% vs . 31.82%, p = 0.029). The viral clearance time was shorter in the AZV+DXM group than in the DXM group (7.32 ± 2.57 vs . 8.55 ± 2.34 days, p = 0.017). The PaO 2 /FiO 2 levels on day 5 (258.89 ± 55.22 vs . 233.12 ± 60.51, p = 0.026) and day 10 (289.48 ± 44.09 vs . 261.52 ± 37.34, p = 0.015) were higher in the AZV+DXM group than the DXM group. However, data on the hospitalization duration of the two groups were similar. Cox analysis showed the benefit of AZV+DXM in the subgroups of ≥65 years old, multiple organ dysfunction syndrome (MODS), cerebrovascular disease, C-reactive protein (CRP) ≥70mg/L, and D-dimer ≥1 µg/L. Conclusion This study is the first to indicate that treatment with AZV+DXM might benefit severe Omicron-infected patients compared with DXM treatment alone. This finding demonstrates, at least partly, the necessity of antiviral treatment in severe patients.

Meng-Lan Zhang

Xiao-Ying Wei

Nan Su

Jung-Hong Jiang

Guo-Peng Xu

Da-Xiong Zeng

Efficacy of azvudine plus dexamethasone in severe hospitalized patients with Omicron infection: a prospective multicenter study

阿兹夫定联合地塞米松治疗奥密克戎感染重症住院患者的疗效：一项前瞻性多中心研究

Introduction Long COVID (LC) poses a persistent challenge in clinical practice due to limited understanding of its etiology. LC is hypothesized to stem from aberrant immune responses in COVID-19. Vaccinations, which boost immune cells to restore function, could help ease LC symptoms. Methods To exclude the impact of vaccination, we examined the immune cell profiles of recovering COVID-19 patients before vaccines were available. White blood cell differentials were monitored in ninety-twohealthy unvaccinated controls. Seventy-six unvaccinated COVID-19 patients were monitored upon admission and on the 50th day post-symptom onset (DPSO50). Peripheral lymphocyte subsets were analyzed using flow cytometry. Results Mild cases showed no significant changes in lymphocyte counts or subsets from admission to DPSO50. By DPSO50, severe and critical cases showed almost complete recovery from lymphopenia, with critical cases having CD19+ B-cell counts approximately 45% lower than the mild group. Severe and critical cases exhibited reduced B-cell frequencies, with critical cases displaying around 48% higher natural killer (NK) cell counts. In mild cases, NK cell counts negatively correlated with B-cell counts (r=-0.528, p=0.02). Additionally, critical cases showed positive correlations between NK cell counts and CD4+ T-cell counts (r=0.83, p&amp;lt;0.01), and between NK cell counts and CD8+ T-cell counts (r=0.74, p&amp;lt;0.01). Severe cases demonstrated decreased counts of CD4+CD25+CD127lowFoxP3+ regulatory T-cells (Tregs), which positively correlated with B-cell counts (r=0.37, p&amp;lt;0.05). Discussion Our findings indicate that aberrant immune cell profiles in COVID-19 patients change dynamically during recovery, depending on disease severity. This study suggests that convalescent patients from critical COVID-19 may experience long-lasting B-cell lymphopenia.

Hui An

Ting Li

Xinyue Zhang

Hao Hu

Chen Zhang

Yongyu Wang

Shengwei Jin

Ming Li

Persistent CD19+ B cell lymphopenia in critically ill COVID-19 patients 50 days after symptom onset

重症COVID-19患者症状出现50天后持续性CD19+ B细胞淋巴细胞减少

The zoonotic pathogen Bartonella henselae is responsible for diverse human diseases, from mild to life-threatening, but it often eludes detection in culture-based assays. This study investigates the potential of B. henselae to enter a viable but nonculturable (VBNC) state when exposed to human fever temperature or antibiotics, with this state confirmed by successful resuscitation. Viability was assessed using SYBR Green I/PI staining and propidium monoazide–quantitative polymerase chain reaction (PMA-qPCR), while culturability was determined through colony-forming unit (CFU) counting on blood agar plates. Resuscitation of VBNC cells was attempted using modified Schneider’s medium with 10% defibrillated sheep blood. In the results, B. henselae cells entered a VBNC state after 19 days of exposure to 38.8°C. Antibiotics, particularly with bactericidal activity, induced the VBNC state within 4 days treatment. Successful resuscitation confirmed the VBNC state developed via the above two strategies. Transmission electron microscopy (TEM) examination revealed intact cell structures and dense cytosol in VBNC cells, with a significant increase in plasmolytic cells. Notably, VBNC cells demonstrated greater drug tolerance than cells in the stationary phase, which encompassed a substantial portion of persisters. Proteomic analysis revealed the up-regulation of proteins linked to host cell invasion and stress resistance, while proteins related to signaling and cellular processes were down-regulated. Fluorescence in situ hybridization (FISH) analysis confirmed that the VBNC state truly boosted B. henselae ’s invasion of HUVECs. This study highlights B. henselae ’s capacity to enter a VBNC state under thermal and antibiotic stress, emphasizing the urgent need for advanced diagnostic and therapeutic strategies to effectively target VBNC cells, which complicate diagnosis and treatment.

Yuze Gou

Dongxia Liu

Yuxian Xin

Ting Wang

Jiaxin Li

Yiwen Xi

Xiaoling Zheng

Tuanjie Che

Ying Zhang

Tingting Li

Jie Feng

Viable but nonculturable state in the zoonotic pathogen Bartonella henselae induced by low-grade fever temperature and antibiotic treatment

低热温度和抗生素处理诱导的动物源性病原菌汉赛巴通体可存活但不可培养状态

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Frontiers in Cellular and Infection Microbiology

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Bacteriocin-Producing Probiotic Lactic Acid Bacteria in Controlling Dysbiosis of the Gut Microbiota

Case Report: Mycobacterium kansasii causing infective endocarditis explored by metagenomic next-generation sequencing

Application of metagenomic next-generation sequencing in patients with infective endocarditis

Research progress on complications of Brucellosis

Shedding light on negative cultures in osteoarticular infections: leveraging mNGS to unravel risk factors and microbial profiles

Shedding light on negative cultures in osteoarticular infections: leveraging mNGS to unravel risk factors and microbial profiles

Interaction between coronaviruses and the autophagic response

Efficacy of azvudine plus dexamethasone in severe hospitalized patients with Omicron infection: a prospective multicenter study

Persistent CD19+ B cell lymphopenia in critically ill COVID-19 patients 50 days after symptom onset

Viable but nonculturable state in the zoonotic pathogen Bartonella henselae induced by low-grade fever temperature and antibiotic treatment