Insights into the epidemiology, pathogenesis, and differential diagnosis of schistosomiasis.

Schistosomiasis is a neglected tropical disease that is prevalent in low- and middle-income countries. There are five human pathogenic species, of which Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum are the most prevalent worldwide and cause the greatest burden of disease in terms of mortality and morbidity. In addition, hybrid schistosomes have been identified through molecular analysis. Human infection occurs when cercariae, the larval form of the parasite, penetrate the skin of people while bathing in contaminated waters such as lakes and rivers. Schistosomiasis can cause both urogenital and intestinal symptoms. Urogenital symptoms include haematuria, bladder fibrosis, kidney damage, and an increased risk of bladder cancer. Intestinal symptoms may include abdominal pain, sometimes accompanied by diarrhoea and blood in the stool. Schistosomiasis affects more than 250 million people and causes approximately 70 million Disability-Adjusted Life Years (DALYs), mainly in Africa, South America, and Asia. To control infection, it is essential to establish sensitive and specific diagnostic tests for epidemiological surveillance and morbidity reduction. This review provides an overview of schistosomiasis, with a focus on available diagnostic tools for Schistosoma spp. Current molecular detection methods and progress in the development of new diagnostics for schistosomiasis infection are also discussed.

Novel Antimicrobial Approaches to Combat Bacterial Biofilms Associated with Urinary Tract Infections.

Urinary tract infections (UTIs) are prevalent bacterial infections in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, the significant increase in antibiotic resistance in recent years has made many previously effective treatments ineffective. Biofilm on medical equipment in healthcare settings creates a reservoir of pathogens that can easily be transmitted to patients. Urinary catheter infections are frequently observed in hospitals and are caused by microbes that form a biofilm after a catheter is inserted into the bladder. Managing infections caused by biofilms is challenging due to the emergence of antibiotic resistance. Biofilms enable pathogens to evade the host's innate immune defences, resulting in long-term persistence. The incidence of sepsis caused by UTIs that have spread to the bloodstream is increasing, and drug-resistant infections may be even more prevalent. While the availability of upcoming tests to identify the bacterial cause of infection and its resistance spectrum is critical, it alone will not solve the problem; innovative treatment approaches are also needed. This review analyses the main characteristics of biofilm formation and drug resistance in recurrent uropathogen-induced UTIs. The importance of innovative and alternative therapies for combatting biofilm-caused UTI is emphasised.

Tackling Drug-Resistant Tuberculosis: New Challenges from the Old Pathogen Mycobacterium tuberculosis.

Antibiotics have played a crucial role in the reduction in the incidence of TB globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors, and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline in antibiotic development, and different economic and social conditions. In this review, we summarize recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasize that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throughout the community.

The Challenge of Overcoming Antibiotic Resistance in Carbapenem-Resistant Gram-Negative Bacteria: "Attack on Titan".

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multidrug-resistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance genes, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

The Dark Side of Nosocomial Infections in Critically Ill COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as healthcare-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

Urinary Tract Infections: The Current Scenario and Future Prospects.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, occurring in both community and healthcare settings. Although the clinical symptoms of UTIs are heterogeneous and range from uncomplicated (uUTIs) to complicated (cUTIs), most UTIs are usually treated empirically. Bacteria are the main causative agents of these infections, although more rarely, other microorganisms, such as fungi and some viruses, have been reported to be responsible for UTIs. Uropathogenic Escherichia coli (UPEC) is the most common causative agent for both uUTIs and cUTIs, followed by other pathogenic microorganisms, such as Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, and Staphylococcus spp. In addition, the incidence of UTIs caused by multidrug resistance (MDR) is increasing, resulting in a significant increase in the spread of antibiotic resistance and the economic burden of these infections. Here, we discuss the various factors associated with UTIs, including the mechanisms of pathogenicity related to the bacteria that cause UTIs and the emergence of increasing resistance in UTI pathogens.

SARS-CoV-2 Infection in Patients with Cystic Fibrosis: What We Know So Far.

Respiratory infections are the most common and most frequent diseases, especially in children and the elderly, characterized by a clear seasonality and with an incidence that usually tends to decrease with increasing age. These infections often resolve spontaneously, usually without the need for antibiotic treatment and/or with the possible use of symptomatic treatments aimed at reducing overproduction of mucus and decreasing coughing. However, when these infections occur in patients with weakened immune systems and/or underlying health conditions, their impact can become dramatic and in some cases life threatening. The rapid worldwide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has caused concern for everyone, becoming especially important for individuals with underlying lung diseases, such as CF patients, who have always paid close attention to implementing protective strategies to avoid infection. However, adult and pediatric CF patients contract coronavirus infection like everyone else. In addition, although numerous studies were published during the first wave of the pandemic on the risk for patients with cystic fibrosis (CF) to develop severe manifestations when infected with SARS-CoV-2, to date, a high risk has been found only for patients with poorer lung function and post-transplant status. In terms of preventive measures, vaccination remains key. The best protection for these patients is to strengthen preventive measures, such as social distancing and the use of masks. In this review, we aim to summarize and discuss recent advances in understanding the susceptibility of CF individuals to SARS-CoV-2 infection.

Molecular Fingerprinting of the Omicron Variant Genome of SARS-CoV-2 by SERS Spectroscopy.

The continuing accumulation of mutations in the RNA genome of the SARS-CoV-2 virus generates an endless succession of highly contagious variants that cause concern around the world due to their antibody resistance and the failure of current diagnostic techniques to detect them in a timely manner. Raman spectroscopy represents a promising alternative to variants detection and recognition techniques, thanks to its ability to provide a characteristic spectral fingerprint of the biological samples examined under all circumstances. In this work we exploit the surface-enhanced Raman scattering (SERS) properties of a silver dendrite layer to explore, for the first time to our knowledge, the distinctive features of the Omicron variant genome. We obtain a complex spectral signal of the Omicron variant genome where the fingerprints of nucleobases in nucleosides are clearly unveiled and assigned in detail. Furthermore, the fractal SERS layer offers the presence of confined spatial regions in which the analyte remains trapped under hydration conditions. This opens up the prospects for a prompt spectral identification of the genome in its physiological habitat and for a study on its activity and variability.

Recent Advances in the Use of Molecular Methods for the Diagnosis of Bacterial Infections.

Infections caused by bacteria have a major impact on public health-related morbidity and mortality. Despite major advances in the prevention and treatment of bacterial infections, the latter continue to represent a significant economic and social burden worldwide. The WHO compiled a list of six highly virulent multidrug-resistant bacteria named ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) responsible for life-threatening diseases. Taken together with Clostridioides difficile, Escherichia coli, Campylobacter spp., (C. jejuni and C. coli), Legionella spp., Salmonella spp., and Neisseria gonorrhoeae, all of these microorganisms are the leading causes of nosocomial infections. The rapid and accurate detection of these pathogens is not only important for the early initiation of appropriate antibiotic therapy, but also for resolving outbreaks and minimizing subsequent antimicrobial resistance. The need for ever-improving molecular diagnostic techniques is also of fundamental importance for improving epidemiological surveillance of bacterial infections. In this review, we aim to discuss the recent advances on the use of molecular techniques based on genomic and proteomic approaches for the diagnosis of bacterial infections. The advantages and limitations of each of the techniques considered are also discussed.

Extended-spectrum ß-lactamase & carbapenemase-producing fermentative Gram-negative bacilli in clinical isolates from a University Hospital in Southern Italy.

The aim of this study was to determine the prevalence of extended-spectrum ß-lactamases (ESBLs)- and carbapenemase-producing fermentative Gram-negative bacteria (FGNB) in a University Hospital in Southern Italy. These bacteria have the potential to disseminate bacterial resistance in healthcare settings and cause untreatable and prolonged infections associated with high rates of mortality. A retrospective observational study was carried out in a University Hospital in Sicily from January to December 2019. A total of 1046 FGNB were recovered from different clinical samples among which 40%, 15% and 37% were, respectively, MDR, carbapenemase and ESBL producers. Antibiotic resistance profile of FGNB against the first-line drugs was remarkably high. K. pneumoniae (57%) followed by E. coli (27%) were found here as the major sources of ESBL producers. The highest proportion of ESBL producers was from ICU ward (72%), and were isolated from urine samples (63.6%) followed by blood samples (54%). Carbapenemase production among the FGNB in our study was about 0.9%, which is more than twice than the prevalence rate reported by the European Antimicrobial Resistance Surveillance Network (ECDC) (0.4%). To our knowledge, this is the first report on the prevalence of ESBL and carbapenemase-producing FGNB in this region. Our data clearly indicate the importance of implementing antibiotic stewardship strategies in our region to reduce the unnecessary use of antibiotics.

Bacterial Antibiotic Resistance: The Most Critical Pathogens.

Antibiotics have made it possible to treat bacterial infections such as meningitis and bacteraemia that, prior to their introduction, were untreatable and consequently fatal. Unfortunately, in recent decades overuse and misuse of antibiotics as well as social and economic factors have accelerated the spread of antibiotic-resistant bacteria, making drug treatment ineffective. Currently, at least 700,000 people worldwide die each year due to antimicrobial resistance (AMR). Without new and better treatments, the World Health Organization (WHO) predicts that this number could rise to 10 million by 2050, highlighting a health concern not of secondary importance. In February 2017, in light of increasing antibiotic resistance, the WHO published a list of pathogens that includes the pathogens designated by the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) to which were given the highest "priority status" since they represent the great threat to humans. Understanding the resistance mechanisms of these bacteria is a key step in the development of new antimicrobial drugs to tackle drug-resistant bacteria. In this review, both the mode of action and the mechanisms of resistance of commonly used antimicrobials will be examined. It also discusses the current state of AMR in the most critical resistant bacteria as determined by the WHO's global priority pathogens list.

The Relevance of IL-1-Signaling in the Protection against Gram-Positive Bacteria.

Previous studies performed using a model of group B streptococcus (GBS)-induced peritoneal inflammation indicate that the interleukin-1 receptor (IL-1R) family plays an important role in the innate host defense against this encapsulated Gram-positive bacteria. Since the role of IL-1-dependent signaling in peritoneal infections induced by other Gram-positive bacteria is unknown, in the present study we sought to investigate the contribution of IL-1R signaling in host defenses against Streptococcus pyogenes (group A streptococcus or GAS) or Staphylococcus aureus, two frequent and global human Gram-positive extracellular pathogens. We analyzed here the outcome of GAS or S. aureus infection in IL-1R-deficient mice. After inoculated intraperitoneal (i.p.) inoculation with group A Streptococcus or S. aureus, all the wild-type (WT) control mice survived the challenge, while, respectively, 63% or 50% of IL-1-defective mice died. Lethality was due to the ability of both bacterial species to replicate and disseminate to the target organs of IL-1R-deficient mice. Moreover, the experimental results indicate that IL-1 signaling promotes the production of leukocyte attractant chemokines CXCL-1 and CXCL-2 and recruitment of neutrophils to bacterial infection sites. Accordingly, the reduced neutrophil recruitment in IL-1R-deficient mice was linked with decreased production of neutrophil chemokines. Collectively, our findings indicate that IL-1 signaling, as previously showed in host defense against GBS, plays a fundamental role also in controlling the progression and outcome of GAS or S. aureus disease.

Correct management and low rate of contagiousness of healthcare workers in a University Hospital in Southern Italy: from contact tracing to serological investigation.

The COVID-19 epidemic, which began in Wuhan in December 2019, quickly spread all over the world, leading in a few months to a high number of deaths also in healthcare workers. The purpose of the study is to a) describe the importance of a correct management of SARS-CoV-2 infections; b) report the number of positive healthcare workers after the epidemic phase and to describe their socio-characteristics data, the main methods of transmission and the symptoms; c) to report the seroconversion rate of healthcare workers  (HCWs). The study was conducted from March 9, 2020 to June 19, 2020 in three phases:1) in a first phase, we implemented the guidelines to be followed for patient care in our hospital; 2) in a second phase, we provided the epidemiological investigation/contact tracing of HCWs; 3)  we collected swabs on all healthcare workers and we also performed serological investigation. The number of healthcare workers under surveillance is of 2611 subjects and, of these, only 0.65% contracted COVID-19. In particular, 70.6% of these have been infected in the healthcare setting, 11, 8% in the family and 17.6% returning from high risk areas. Ultimately, only 0.1% of HCWs dedicated to the treatment of COVID-19 patients contracted the infection (one was asymptomatic). Only 2% of HCWS were positive for serological investigation.

Characterization of an immunogenic cellulase secreted by Cryptococcus pathogens.

Members of the C. neoformans/C. gattiii species complex are an important cause of serious humans infections, including meningoencephalitis. We describe here a 45 kDa extracellular cellulase purified from culture supernatants of C. neoformans var. neoformans. The N-terminal sequence obtained from the purified protein was used to isolate a clone containing the full-length coding sequence from a C. neoformans var. neoformans (strain B-3501A) cDNA library. Bioinformatics analysis indicated that this gene is present, with variable homology, in all sequenced genomes of the C. neoformans/C. gattii species complex. The cDNA clone was used to produce a recombinant 45 kDa protein in E. coli that displayed the ability to convert carboxymethyl cellulose and was therefore designated as NG-Case (standing for Neoformans Gattii Cellulase). To explore its potential use as a vaccine candidate, the recombinant protein was used to immunize mice and was found capable of inducing T helper type 1 responses and delayed-type hypersensitivity reactions, but not immune protection against a highly virulent C. neoformans var grubii strain. These data may be useful to better understand the mechanisms underlying the ability C. neoformans/C. gattii to colonize plant habitats and to interact with the human host during infection.

Nucleic Acid-Sensing Toll-Like Receptors Play a Dominant Role in Innate Immune Recognition of Pneumococci.

Streptococcus pneumoniae (or pneumococcus) is a highly prevalent human pathogen. Toll-like receptors (TLRs) function as immune sensors that can trigger host defenses against this bacterium. Defects in TLR-activated signaling pathways, including deficiency in the adaptor protein myeloid differentiation factor 88 (MyD88), are associated with markedly increased susceptibility to infection. However, the individual MyD88-dependent TLRs predominantly involved in antipneumococcal defenses have not been identified yet. Here we find that triple knockout mice simultaneously lacking TLR7, TLR9, and TLR13, which sense the presence of bacterial DNA (TLR9) and RNA (TLR7 and TLR13) in the phagolysosomes of phagocytic cells, display a phenotype that largely resembles that of MyD88-deficient mice and rapidly succumb to pneumococcal pneumonitis due to defective neutrophil influx into the lung. Accordingly, TLR7/9/13 triple knockout resident alveolar macrophages were largely unable to respond to pneumococci with the production of neutrophil-attracting chemokines and cytokines. Mice with single deficiencies of TLR7, TLR9, or TLR13 showed unaltered ability to control lung infection but were moderately more susceptible to encephalitis, in association with a decreased ability of microglia to mount cytokine responses in vitro Our data point to a dominant, tissue-specific role of nucleic acid-sensing pathways in innate immune recognition of S. pneumoniae and also show that endosomal TLRs are largely capable of compensating for the absence of each other, which seems crucial to prevent pneumococci from escaping immune recognition. These results may be useful to develop novel strategies to treat infections by antibiotic-resistant pneumococci based on stimulation of the innate immune system.IMPORTANCE The pneumococcus is a bacterium that frequently causes infections in the lungs, ears, sinus cavities, and meninges. During these infections, body defenses are triggered by tissue-resident cells that use specialized receptors, such as Toll-like receptors (TLRs), to sense the presence of bacteria. We show here that pneumococci are predominantly detected by TLRs that are located inside intracellular vacuoles, including endosomes, where these receptors can sense the presence of nucleic acids released from ingested bacteria. Mice that simultaneously lacked three of these receptors (specifically, TLR7, TLR9, and TLR13) were extremely susceptible to lung infection and rapidly died after inhalation of pneumococci. Moreover, tissue-resident macrophages from these mice were impaired in their ability to respond to the presence of pneumococci by producing inflammatory mediators capable of recruiting polymorphonuclear leucocytes to infection sites. This information may be useful to develop drugs to treat pneumococcal infections, particularly those caused by antibiotic-resistant strains.

Neutrophils Enhance Their Own Influx to Sites of Bacterial Infection via Endosomal TLR-Dependent Cxcl2 Production.

The influx of neutrophils to infection sites is a fundamental step in host defenses against the frequent human pathogen group B Streptococcus (GBS) and other extracellular bacteria. Using a mouse model of GBS-induced peritonitis, we show in this study that the chemokines Cxcl1 and Cxcl2 play distinctive roles in enhancing the recruitment and the antibacterial activities of neutrophils in a manner that is linked to differences in the cellular sources of these mediators. Cell depletion experiments demonstrated that neutrophils make a significant contribution to the in vivo production of Cxcl2 but not Cxcl1. In vitro, neutrophils responded weakly to LPS but released high levels of Cxcl2 after stimulation with GBS or other bacteria. Neutrophil-derived Cxcl2 acted in an autocrinous manner to increase its own production and to enhance antibacterial activities, including the release of oxygen radicals. In both neutrophils and macrophages, the production of Cxcl1/2 largely required the presence of functional UNC93B1, a chaperone protein involved in signaling by endosomal TLRs. Moreover, the phenotype of UNC93B1-defective phagocytes could be recapitulated by the simultaneous absence of TLR7, 9, and 13 but not by the absence of individual TLRs. Collectively, our data show that neutrophils recognize Gram-positive and Gram-negative bacteria by means of multiple phagosomal TLRs, resulting in de novo synthesis of Cxcl2, amplification of neutrophil recruitment, and potentiation of their antibacterial activities. These data may be useful to devise alternative therapeutic strategies aimed at enhancing the recruitment and the functional activities of polymorphonuclear leukocytes during infections caused by antibiotic-resistant bacteria.

The plasminogen binding protein PbsP is required for brain invasion by hypervirulent CC17 Group B streptococci.

Streptococcus agalactiae (Group B Streptococcus or GBS) is a frequent cause of serious disease in newborns and adults. Epidemiological evidence indicates a strong association between GBS strains belonging to the hypervirulent CC17 clonal complex and the occurrence of meningitis in neonates. We investigate here the role of PbsP, a cell wall plasminogen binding protein, in colonization of the central nervous system by CC17 GBS. Deletion of pbsP selectively impaired the ability of the CC17 strain BM110 to colonize the mouse brain after intravenous challenge, despite its unchanged capacity to persist at high levels in the blood and to invade the kidneys. Moreover, immunization with a recombinant form of PbsP considerably reduced brain infection and lethality. In vitro, pbsP deletion markedly decreased plasmin-dependent transmigration of BM110 through brain microvascular endothelial cells. Although PbsP was modestly expressed in bacteria grown under standard laboratory conditions, pbsP expression was markedly upregulated during in vivo infection or upon contact with cultured brain endothelial cells. Collectively, our studies indicate that PbsP is a highly conserved Plg binding adhesin, which is functionally important for invasion of the central nervous system by the hypervirulent CC17 GBS. Moreover, this antigen is a promising candidate for inclusion in a universal GBS vaccine.

Therapeutic potential of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice by targeting IL-1ß and IL-18.

Interleukin (IL)-1 and IL-18 belong to the IL-1 family of ligands, and their receptors are members of the IL-1 receptor family. Both cytokines drive an extensive range of pro-inflammatory networks in many cell types using common signal transduction cascades. Anyway, differences in signaling pathways exist. With this aim in mind, we investigated by using transgenic mice the mechanisms through the simultaneous deficiency of both IL-1ß and IL-18 could be more protective compared to blocking the single cytokine IL-1ß or IL-18 during colitis. Colitis was provoked in mice by instillation of dinitrobenzene sulfonic acid (DNBS) in the colon. The results indicated that single knockout (KO) mice of IL-1ß or IL-18, and double KO mice of both IL-1ß and IL-18 were hyporesponsive to DNBS-induced colitis compared to wild type (WT) mice, in which double KO were less sensitive than single KO mice. Moreover, treatment with Anakinra (IL-1R antagonist) also ameliorated colitis, in views of macroscopic and histological alteration, infiltration of neutrophils or Th1 cells, oxidative and nitrosative stress. Anakinra more significantly reduced cyclooxygenase (COX-2) and nuclear factor (NF-κB) levels as well as IKB-α degradation compared to blocking IL-18. On the contrary, the absence of IL-18 reduced p-ERK and p-p38 mitogen-activated protein kinase (MAPKs) in a more significant way compared to blocking IL-1ß. Thus, the double KO increased the protective effects against colon inflammation maybe because different converging inflammatory pathways are being inhibited. In conclusion, the blocking of both IL-1ß and IL-18 function may be advantageous in the treatment of IBD or inflammatory diseases.

The Streptococcus agalactiae cell wall-anchored protein PbsP mediates adhesion to and invasion of epithelial cells by exploiting the host vitronectin/αv integrin axis.

Binding of microbial pathogens to host vitronectin (Vtn) is a common theme in the pathogenesis of invasive infections. In this study, we characterized the role of Vtn in the invasion of mucosal epithelial cells by Streptococcus agalactiae (i.e. group B streptococcus or GBS), a frequent human pathogen. Moreover, we identified PbsP, a previously described plasminogen-binding protein of GBS, as a dual adhesin that can also interact with human Vtn through its streptococcal surface repeat (SSURE) domains. Deletion of the pbsP gene decreases both bacterial adhesion to Vtn-coated inert surfaces and the ability of GBS to interact with epithelial cells. Bacterial adherence to and invasion of epithelial cells were either inhibited or enhanced by cell pretreatment with, respectively, anti-Vtn antibodies or Vtn, confirming the role of Vtn as a GBS ligand on host cells. Finally, antibodies directed against the integrin αv subunit inhibited Vtn-dependent cell invasion by GBS. Collectively, these results indicate that Vtn acts as a bridge between the SSURE domains of PbsP on the GBS surface and host integrins to promote bacterial invasion of epithelial cells. Therefore, inhibition of interactions between PbsP and extracellular matrix components could represent a viable strategy to prevent colonization and invasive disease by GBS.