Protective Activity of Streptococcus pneumoniae Spr1875 Protein Fragments Identified Using a Phage Displayed Genomic Library

There is considerable interest in pneumococcal protein antigens capable of inducing serotype-independent immunoprotection and of improving, thereby, existing vaccines. We report here on the immunogenic properties of a novel surface antigen encoded by ORF spr1875 in the R6 strain genome. An antigenic fragment encoded by spr1875, designated R4, was identified using a Streptococcus pneumoniae phage displayed genomic library after selection with a human convalescent serum. Immunofluorescence analysis with anti-R4 antisera showed that Spr1875 was expressed on the surface of strains belonging to different serotypes. Moreover, the gene was present with little sequence variability in 27 different pneumococcal strains isolated worldwide. A mutant lacking Spr1875 was considerably less virulent than the wild type D39 strain in an intravenous mouse model of infection. Moreover, immunization with the R4 recombinant fragment, but not with the whole Spr1875 protein, induced significant protection against sepsis in mice. Lack of protection after immunization with the whole protein was related to the presence of immunodominant, non-protective epitopes located outside of the R4 fragment. In conclusion, our data indicate that Spr1875 has a role in pneumococcal virulence and is immunogenic. As the R4 fragment conferred immunoprotection from experimental sepsis, selected antigenic fragments of Spr1875 may be useful for the development of a pneumococcal protein-based vaccine

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

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

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

Tackling Drug-Resistant Tuberculosis: New Challenges from the Old Pathogen <i>Mycobacterium tuberculosis</i>

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 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

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

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

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