Infection and Immunity最新文献

{"title":"Triple threat: how diabetes results in worsened bacterial infections.","authors":"Benjamin P Darwitz, Christopher J Genito, Lance R Thurlow","doi":"10.1128/iai.00509-23","DOIUrl":"10.1128/iai.00509-23","url":null,"abstract":"<p><p>Diabetes mellitus, characterized by impaired insulin signaling, is associated with increased incidence and severity of infections. Various diabetes-related complications contribute to exacerbated bacterial infections, including hyperglycemia, innate immune cell dysfunction, and infection with antibiotic-resistant bacterial strains. One defining symptom of diabetes is hyperglycemia, resulting in elevated blood and tissue glucose concentrations. Glucose is the preferred carbon source of several bacterial pathogens, and hyperglycemia escalates bacterial growth and virulence. Hyperglycemia promotes specific mechanisms of bacterial virulence known to contribute to infection chronicity, including tissue adherence and biofilm formation. Foot infections are a significant source of morbidity in individuals with diabetes and consist of biofilm-associated polymicrobial communities. Bacteria perform complex interspecies behaviors conducive to their growth and virulence within biofilms, including metabolic cross-feeding and altered phenotypes more tolerant to antibiotic therapeutics. Moreover, the metabolic dysfunction caused by diabetes compromises immune cell function, resulting in immune suppression. Impaired insulin signaling induces aberrations in phagocytic cells, which are crucial mediators for controlling and resolving bacterial infections. These aberrancies encompass altered cytokine profiles, the migratory and chemotactic mechanisms of neutrophils, and the metabolic reprogramming required for the oxidative burst and subsequent generation of bactericidal free radicals. Furthermore, the immune suppression caused by diabetes and the polymicrobial nature of the diabetic infection microenvironment may promote the emergence of novel strains of multidrug-resistant bacterial pathogens. This review focuses on the \"triple threat\" linked to worsened bacterial infections in individuals with diabetes: (i) altered nutritional availability in diabetic tissues, (ii) diabetes-associated immune suppression, and (iii) antibiotic treatment failure.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-framing the importance of Group B <i>Streptococcus</i> as a gut-resident pathobiont.","authors":"Joie Ling, Andrew J Hryckowian","doi":"10.1128/iai.00478-23","DOIUrl":"10.1128/iai.00478-23","url":null,"abstract":"<p><p><i>Streptococcus agalactiae</i> (Group B <i>Streptococcus</i>, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage fate: to kill or not to kill?","authors":"Armando M Marrufo, Ana Lidia Flores-Mireles","doi":"10.1128/iai.00476-23","DOIUrl":"10.1128/iai.00476-23","url":null,"abstract":"<p><p>Macrophages are dynamic innate immune cells that either reside in tissue, serving as sentinels, or recruited as monocytes from bone marrow into inflamed and infected tissue. In response to cues in the tissue microenvironment (TME), macrophages polarize on a continuum toward M1 or M2 with diverse roles in progression and resolution of disease. M1-like macrophages exhibit proinflammatory functions with antimicrobial and anti-tumorigenic activities, while M2-like macrophages have anti-inflammatory functions that generally resolve inflammatory responses and orchestrate a tissue healing process. Given these opposite phenotypes, proper spatiotemporal coordination of macrophage polarization in response to cues within the TME is critical to effectively resolve infectious disease and regulate wound healing. However, if this spatiotemporal coordination becomes disrupted due to persistent infection or dysregulated coagulation, macrophages' inappropriate response to these cues will result in the development of diseases with clinically unfavorable outcomes. Since plasticity and heterogeneity are hallmarks of macrophages, they are attractive targets for therapies to reprogram toward specific phenotypes that could resolve disease and favor clinical prognosis. In this review, we discuss how basic science studies have elucidated macrophage polarization mechanisms in TMEs during infections and inflammation, particularly coagulation. Therefore, understanding the dynamics of macrophage polarization within TMEs in diseases is important in further development of targeted therapies.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophils as drivers of bacterial immunomodulation and persistence.","authors":"Katelyn M Parrish, Monica C Gestal","doi":"10.1128/iai.00175-24","DOIUrl":"10.1128/iai.00175-24","url":null,"abstract":"<p><p>Traditionally, eosinophils have been linked to parasitic infections and pathological disease states. However, emerging literature has unveiled a more nuanced and intricate role for these cells, demonstrating their key functions in maintaining mucosal homeostasis. Eosinophils exhibit diverse phenotypes and exert multifaceted effects during infections, ranging from promoting pathogen persistence to triggering allergic reactions. Our investigations primarily focus on <i>Bordetella</i> spp., with particular emphasis on <i>Bordetella bronchiseptica</i>, a natural murine pathogen that induces diseases in mice akin to pertussis in humans. Recent findings from our published work have unveiled a striking interaction between <i>B. bronchiseptica</i> and eosinophils, facilitated by the <i>btrS</i>-mediated mechanism. This interaction serves to enhance pathogen persistence while concurrently delaying adaptive immune responses. Notably, this role of eosinophils is only noted in the absence of a functional <i>btrS</i> signaling pathway, indicating that wild-type <i>B. bronchiseptica</i>, and possibly other <i>Bordetella</i> spp., possess such adeptness in manipulating eosinophils that the true function of these cells remains obscured during infection. In this review, we present the mounting evidence pointing toward eosinophils as targets of bacterial exploitation, facilitating pathogen persistence and fostering chronic infections in diverse mucosal sites, including the lungs, gut, and skin. We underscore the pivotal role of the master regulator of <i>Bordetella</i> pathogenesis, the sigma factor BtrS, in orchestrating eosinophil-dependent immunomodulation within the context of pulmonary infection. These putative convergent strategies of targeting eosinophils offer promising avenues for the development of novel therapeutics targeting respiratory and other mucosal pathogens.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic diversification of the gut commensal Providencia alcalifaciens via acquisition of a second type III secretion system","authors":"Jessica A. KleinAlexander V. PredeusAimee R. GreisslMattie M. Clark-HerreraEddy CruzJennifer A. CundiffAmanda L. HaeberleMaya HowellAaditi LeleDonna J. RobinsonTrina L. WestermanMarie WrandeSarah J. WrightNicole M. GreenBruce A. VallanceMichael McClellandAndres MejiaAlan G. GoodmanJohanna R. ElfenbeinLeigh A. Knodler1Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA2Wellcome Sanger Institute, Hinxton, Cambridgeshire, United Kingdom3Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA4Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA5Public Health Laboratory, Los Angeles County Department of Public Health, Downey, California, USA6Division of Gastroenterology, Hepatology and Nutrition, BC Children’s Hospital and the University of British Columbia, Vancou..","doi":"10.1128/iai.00314-24","DOIUrl":"https://doi.org/10.1128/iai.00314-24","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T6SS in plant pathogens: unique mechanisms in complex hosts.","authors":"Lexie M Matte, Abigail V Genal, Emily F Landolt, Elizabeth S Danka","doi":"10.1128/iai.00500-23","DOIUrl":"10.1128/iai.00500-23","url":null,"abstract":"<p><p>Type VI secretion systems (T6SSs) are complex molecular machines that allow bacteria to deliver toxic effector proteins to neighboring bacterial and eukaryotic cells. Although initial work focused on the T6SS as a virulence mechanism of human pathogens, the field shifted to examine the use of T6SSs for interbacterial competition in various environments, including in the plant rhizosphere. Genes encoding the T6SS are estimated to be found in a quarter of all Gram-negative bacteria and are especially highly represented in <i>Proteobacteria</i>, a group which includes the most important bacterial phytopathogens. Many of these pathogens encode multiple distinct T6SS gene clusters which can include the core components of the apparatus as well as effector proteins. The T6SS is deployed by pathogens at multiple points as they colonize their hosts and establish an infection. In this review, we describe what is known about the use of T6SS by phytopathogens against plant hosts and non-plant organisms, keeping in mind that the structure of plants requires unique mechanisms of attack that are distinct from the mechanisms used for interbacterial interactions and against animal hosts. While the interactions of specific effectors (such as phospholipases, endonucleases, peptidases, and amidases) with targets have been well described in the context of interbacterial competition and in some eukaryotic interactions, this review highlights the need for future studies to assess the activity of phytobacterial T6SS effectors against plant cells.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Noh et al., “Identification of Anaplasma marginale adhesins for entry into Dermacentor andersoni tick cells using phage display”","authors":"Susan M. NohJessica UjczoDebra C. AlperinShelby M. JarvisMuna S. M. SolymanRoberta KokuOlalekan C. AkinsulieElizabeth J. Hoffmann","doi":"10.1128/iai.00377-24","DOIUrl":"https://doi.org/10.1128/iai.00377-24","url":null,"abstract":"Infection and Immunity, Ahead of Print. <br/>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The type II secretion system as an underappreciated and understudied mediator of interbacterial antagonism.","authors":"Nicholas P Cianciotto","doi":"10.1128/iai.00207-24","DOIUrl":"10.1128/iai.00207-24","url":null,"abstract":"<p><p>Interbacterial antagonism involves all major phyla, occurs across the full range of ecological niches, and has great significance for the environment, clinical arena, and agricultural and industrial sectors. Though the earliest insight into interbacterial antagonism traces back to the discovery of antibiotics, a paradigm shift happened when it was learned that protein secretion systems (e.g., types VI and IV secretion systems) deliver toxic \"effectors\" against competitors. However, a link between interbacterial antagonism and the Gram-negative type II secretion system (T2SS), which exists in many pathogens and environmental species, is not evident in prior reviews on bacterial competition or T2SS function. A current examination of the literature revealed four examples of a T2SS or one of its known substrates having a bactericidal activity against a Gram-positive target or another Gram-negative. When further studied, the T2SS effectors proved to be peptidases that target the peptidoglycan of the competitor. There are also reports of various bacteriolytic enzymes occurring in the culture supernatants of some other Gram-negative species, and a link between these bactericidal activities and T2SS is suggested. Thus, a T2SS can be a mediator of interbacterial antagonism, and it is possible that many T2SSs have antibacterial outputs. Yet, at present, the T2SS remains relatively understudied for its role in interbacterial competition. Arguably, there is a need to analyze the T2SSs of a broader range of species for their role in interbacterial antagonism. Such investigation offers, among other things, a possible pathway toward developing new antimicrobials for treating disease.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of cold shock proteins B and D in <i>Aeromonas salmonicida</i> subsp. <i>salmonicida</i> physiology and virulence in lumpfish (<i>Cyclopterus lumpus</i>).","authors":"Ahmed Hossain, Hajarooba Gnanagobal, Trung Cao, Setu Chakraborty, Joy Chukwu-Osazuwa, Manuel Soto-Dávila, Ignacio Vasquez, Javier Santander","doi":"10.1128/iai.00011-24","DOIUrl":"10.1128/iai.00011-24","url":null,"abstract":"<p><p>Cold shock proteins (Csp) are pivotal nucleic acid binding proteins known for their crucial roles in the physiology and virulence of various bacterial pathogens affecting plant, insect, and mammalian hosts. However, their significance in bacterial pathogens of teleost fish remains unexplored. <i>Aeromonas salmonicida</i> subsp. <i>salmonicida</i> (hereafter <i>A. salmonicida</i>) is a psychrotrophic pathogen and the causative agent of furunculosis in marine and freshwater fish. Four <i>csp</i> genes (<i>cspB, cspD, cspA</i>, and <i>cspC</i>) have been identified in the genome of <i>A. salmonicida</i> J223 (wild type). Here, we evaluated the role of DNA binding proteins, CspB and CspD, in <i>A. salmonicida</i> physiology and virulence in lumpfish (<i>Cyclopterus lumpus</i>). <i>A. salmonicida</i> Δ<i>cspB</i>, Δ<i>cspD</i>, and the double Δ<i>cspB</i>Δ<i>cspD</i> mutants were constructed and characterized. <i>A. salmonicida</i> Δ<i>cspB</i> and Δ<i>cspB</i>Δ<i>cspD</i> mutants showed a faster growth at 28°C, and reduced virulence in lumpfish. <i>A. salmonicida</i> Δ<i>cspD</i> showed a slower growth at 28°C, biofilm formation, lower survival in low temperatures and freezing conditions (-20°C, 0°C, and 4°C), deficient in lipopolysaccharide synthesis, and low virulence in lumpfish. Additionally, Δ<i>cspB</i>Δ<i>cspD</i> mutants showed less survival in the presence of bile compared to the wild type. Transcriptome analysis revealed that 200, 37, and 921 genes were differentially expressed in Δ<i>cspB</i>, Δ<i>cspD</i>, and Δ<i>cspB</i>Δ<i>cspD,</i> respectively. In Δ<i>cspB</i> and Δ<i>cspB</i>Δ<i>cspD</i> virulence genes in the chromosome and virulence plasmid were downregulated. Our analysis indicates that CspB and CspD mostly act as a transcriptional activator, influencing cell division (e.g., <i>treB</i>), virulence factors (e.g., <i>aexT</i>), and ultimately virulence.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence and metal-ion acquisition gene expression increases during infection with <i>Treponema phagedenis</i> strains from bovine digital dermatitis.","authors":"Colton Scott, Angelica P Dias, Jeroen De Buck","doi":"10.1128/iai.00117-24","DOIUrl":"10.1128/iai.00117-24","url":null,"abstract":"<p><p>Digital dermatitis (DD) is an ulcerative foot lesion on the heel bulbs of dairy cattle. DD is a polymicrobial disease with no precise etiology, although <i>Treponema</i> spirochetes are found disproportionally abundant in diseased tissue. Within <i>Treponema,</i> several different species are found in DD; however, the species <i>Treponema phagedenis</i> is uniformly found in copious quantities and deep within the skin layers of the active, ulcerative stages of disease. The pathogenic mechanisms these bacteria use to persist in the skin and the precise role they play in the pathology of DD are widely unknown. To explore the pathogenesis and virulence of <i>Treponema phagedenis</i>, newly isolated strains of this species were investigated in a subcutaneous murine abscess model. In the first trial, a dosage study was conducted to compare the pathogenicity of different strains across three different treponemes per inoculum (TPI) doses based on abscess volumes. In the second trial, the expression levels of 11 putative virulence genes were obtained to gain insight into their involvement in pathogenesis. During the RT-qPCR analysis, it was determined that genes encoding for two metal-ion import lipoproteins and two adherence genes were found highly upregulated during infection. Conversely, two genes involved in motility and chemotaxis were found to not be significantly upregulated or utilized during infection. These results were supported by gene expression data from natural M2 lesions of dairy cattle. This gene expression analysis could highlight the preference in strategy for <i>T. phagedenis</i> to persist and adhere in the host rather than engage in motility and disseminate.</p>","PeriodicalId":13541,"journal":{"name":"Infection and Immunity","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}