Streptococcus pyogenes Colonization in Children Aged 24-59 Months in the Gambia: Impact of Live Attenuated Influenza Vaccine and Associated Serological Responses.

Background: Immunity to Streptococcus pyogenes in high burden settings is poorly understood. We explored S. pyogenes nasopharyngeal colonization after intranasal live attenuated influenza vaccine (LAIV) among Gambian children aged 24-59 months, and resulting serological response to 7 antigens.

Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of complex.

Lineage 7 (L7) emerged in the phylogeny of the complex (MTBC) subsequent to the branching of 'ancient' lineage 1 and prior to the Eurasian dispersal of 'modern' lineages 2, 3 and 4. In contrast to the major MTBC lineages, the current epidemiology suggests that prevalence of L7 is highly confined to the Ethiopian population, or when identified outside of Ethiopia, it has mainly been in patients of Ethiopian origin. To search for microbiological factors that may contribute to its restricted distribution, we compared the genome of L7 to the genomes of globally dispersed MTBC lineages.

Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer.

Background And Aims: The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.

Methods: A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61).

Introduction of Novel Drug Targets against and Proposing Putative Inhibitors against Adenine N1 (mA22)-tRNA Methyltransferase (TrmK) using Computer-aided Drug Discovery.

Background: Nowadays, the emergence of methicillin-resistant (MRSA) and vancomycin-resistant (VRSA) strains has dramatically restricted the treatment options against this microorganism.

Aim: In this study, we aimed to discover new drug targets and inhibitors against .

Methods: This study consists of two major sections.

Dorzolamide suppresses PKCδ -TIRAP-p38 MAPK signaling axis to dampen the inflammatory response.

Sepsis is a syndrome due to microbial infection causing impaired multiorgan function. Its underlying cause is immune dysfunction and macrophages play an essential role. TIRAP interaction with PKCδ in macrophage was studied, revealing downstream signaling by Western blot and quantitative reverse transcriptase PCR.

COVID-19 Associated Pulmonary Aspergillosis in Patients on Extracorporeal Membrane Oxygenation Treatment-A Retrospective Study.

Background: The incidence and outcome of pulmonary aspergillosis in coronavirus disease (COVID-19) patients on extracorporeal membrane oxygenation (ECMO) are unknown and have not been fully addressed. We investigated the incidence, risk factors and outcome of pulmonary aspergillosis in COVID-19 ECMO patients. In addition, the diagnostic utility of bronchoalveolar lavage fluid and CT scans in this setting were assessed.

Architecture of the biofilm-associated archaic Chaperone-Usher pilus CupE from Pseudomonas aeruginosa.

Chaperone-Usher Pathway (CUP) pili are major adhesins in Gram-negative bacteria, mediating bacterial adherence to biotic and abiotic surfaces. While classical CUP pili have been extensively characterized, little is known about so-called archaic CUP pili, which are phylogenetically widespread and promote biofilm formation by several human pathogens. In this study, we present the electron cryomicroscopy structure of the archaic CupE pilus from the opportunistic human pathogen Pseudomonas aeruginosa.

The F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation.

Conjugation is used by bacteria to propagate antimicrobial resistance (AMR) in the environment. Central to this process are widespread conjugative F-pili that establish the connection between donor and recipient cells, thereby facilitating the spread of IncF plasmids among enteropathogenic bacteria. Here, we show that the F-pilus is highly flexible but robust at the same time, properties that increase its resistance to thermochemical and mechanical stresses.

Systemic Infection Model to Study Altered Virulence during Polymicrobial Infection by .

Background: Polymicrobial infections are complex infections associated with worse outcomes compared to monomicrobial infections. We need simple, fast, and cost-effective animal models to assess their still poorly known pathogenesis.

Methods: We developed a polymicrobial infection model for opportunistic pathogens and assessed its capacity to discriminate the effects of bacterial mixtures taken from cases of human polymicrobial infections by strains.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.

Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing.

Ready, STAT3, Go! Bacteria in the race for M2 macrophage polarisation.

Despite macrophages representing professional immune cells that are integral to the host defences against microbial threats, several intracellular bacteria not only infect, but survive, replicate and often persist in these cells. This is perhaps possible because not all macrophages are the same. Instead, macrophages are loosely divided into two classes: the M1 'classically activated' pro-inflammatory subset and the M2 'alternatively activated' cells that are generally anti-inflammatory and infection-permissive.

XerC Is Required for the Repair of Antibiotic- and Immune-Mediated DNA Damage in Staphylococcus aureus.

To survive in the host environment, pathogenic bacteria need to be able to repair DNA damage caused by both antibiotics and the immune system. The SOS response is a key bacterial pathway to repair DNA double-strand breaks and may therefore be a good target for novel therapeutics to sensitize bacteria to antibiotics and the immune response. However, the genes required for the SOS response in Staphylococcus aureus have not been fully established.

Identification of Putative Drug Targets in Highly Resistant Gram-Negative Bacteria; and Drug Discovery Against Glycyl-tRNA Synthetase as a New Target.

Background: Gram-negative bacterial infections are on the rise due to the high prevalence of multidrug-resistant bacteria, and efforts must be made to identify novel drug targets and then new antibiotics.

Methods: In the upstream part, we retrieved the genome sequences of 4 highly resistant Gram-negative bacteria (e.g.

Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance.

Globally, enteropathogenic bacteria are a major cause of morbidity and mortality. , Shiga-toxin-producing , and are among the top five most commonly reported zoonotic pathogens in the European Union. However, not all individuals naturally exposed to enteropathogens go on to develop disease.

RNA Management During T7 Infection.

Post-transcriptional regulation (PTR) determines the fate of RNA in the cell and represents an important control point in the flow of genetic information and thus underpins many, if not all, aspects of cell function. Host takeover by phages through misappropriation of the bacterial transcription machinery is a relatively advanced area of research. However, several phages encode small regulatory RNAs, which are major mediators of PTR, and produce specific proteins to manipulate bacterial enzymes involved in RNA degradation.

Archaeal DNA-import apparatus is homologous to bacterial conjugation machinery.

Conjugation is a major mechanism of horizontal gene transfer promoting the spread of antibiotic resistance among human pathogens. It involves establishing a junction between a donor and a recipient cell via an extracellular appendage known as the mating pilus. In bacteria, the conjugation machinery is encoded by plasmids or transposons and typically mediates the transfer of cognate mobile genetic elements.

Transcriptional organization and regulation of the K1 type VI secretion system gene cluster.

The type VI secretion system (T6SS) is an antimicrobial molecular weapon that is widespread in Proteobacteria and offers competitive advantages to T6SS-positive micro-organisms. Three T6SSs have recently been described in KT2440 and it has been shown that one, K1-T6SS, is used to outcompete a wide range of phytopathogens, protecting plants from pathogen infections. Given the relevance of this system as a powerful and innovative mechanism of biological control, it is critical to understand the processes that govern its expression.

Transmembrane substrates of type three secretion system injectisomes.

The type three secretion system injectisome of Gram-negative bacterial pathogens injects virulence proteins, called effectors, into host cells. Effectors of mammalian pathogens carry out a range of functions enabling bacterial invasion, replication, immune suppression and transmission. The injectisome secretes two translocon proteins that insert into host cell membranes to form a translocon pore, through which effectors are delivered.

Suppression of innate immunity by the vaccinia virus protein N1 promotes skin microbiota expansion and increased immune infiltration following vaccination.

Vaccinia virus (VACV) protein N1 is an intracellular immunomodulator that contributes to virus virulence via inhibition of NF-κB. Intradermal infection with a VACV lacking gene (vΔN1) results in smaller skin lesions than infection with wild-type virus (WT VACV), but the impact of N1 deletion on the local microbiota as well as the innate and cellular immune responses in infected ear tissue is mostly uncharacterized. Here, we analysed the bacterial burden and host immune response at the site of infection and report that the presence of protein N1 correlated with enhanced expansion of skin microbiota, even before lesion development.

Human serum induces daptomycin tolerance in and viridans group streptococci.

Daptomycin is a membrane-targeting lipopeptide antibiotic used in the treatment of infective endocarditis caused by multidrug-resistant Gram-positive bacteria such as , enterococci and viridans group streptococci. Despite demonstrating excellent activity and a low prevalence of resistant isolates, treatment failure is a significant concern, particularly for enterococcal infection. We have shown recently that human serum triggers daptomycin tolerance in , but it was not clear if a similar phenotype occurred in other major infective endocarditis pathogens.

Growth Arrest of Staphylococcus aureus Induces Daptomycin Tolerance via Cell Wall Remodelling.

Almost all bactericidal drugs require bacterial replication and/or metabolic activity for their killing activity. When these processes are inhibited by bacteriostatic antibiotics, bacterial killing is significantly reduced. One notable exception is the lipopeptide antibiotic daptomycin, which has been reported to efficiently kill growth-arrested bacteria.

Correlates of immunity to Group A Streptococcus: a pathway to vaccine development.

Understanding immunity in humans to Group A Streptococcus (Strep A) is critical for the development of successful vaccines to prevent the morbidity and mortality attributed to Strep A infections. Despite decades of effort, no licensed vaccine against Strep A exists and immune correlates of protection are lacking; a major impediment to vaccine development. In the absence of a vaccine, we can take cues from the development of natural immunity to Strep A in humans to identify immune correlates of protection.