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Seminars in Respiratory and Critical... Dec 2019Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary... (Review)
Review
Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as , methicillin-resistant , and species of the complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.
Topics: Bacterial Infections; Burkholderiaceae; Cystic Fibrosis; Humans; Methicillin-Resistant Staphylococcus aureus; Microbiota; Mycoses; Pseudomonas aeruginosa; Respiratory Tract Infections; Virus Diseases
PubMed: 31887768
DOI: 10.1055/s-0039-1698464 -
Cells Dec 2020The genus includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are , , and... (Review)
Review
The genus includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are , , and the members of the complex (Bcc). and , the cause of glanders and melioidosis, respectively, are considered potential bioweapons. The Bcc comprises a subset of species associated with respiratory infections in people with chronic granulomatous disease and cystic fibrosis. Antimicrobial treatment of infections is difficult due to the intrinsic multidrug antibiotic resistance of these bacteria; prophylactic vaccines provide an attractive alternative to counteract these infections. Although commercial vaccines against infections are still unavailable, substantial progress has been made over recent years in the development of vaccines against and . This review critically discusses the current advances in vaccine development against , and the Bcc.
Topics: Animals; Bacterial Vaccines; Burkholderia; Burkholderia Infections; Humans; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit
PubMed: 33322641
DOI: 10.3390/cells9122671 -
Vaccines Jun 2021Human infections caused by the opportunist pathogens complex and are of particular concern due to their severity, their multiple antibiotic resistance, and the limited... (Review)
Review
Human infections caused by the opportunist pathogens complex and are of particular concern due to their severity, their multiple antibiotic resistance, and the limited eradication efficiency of the current available treatments. New therapeutic options have been pursued, being vaccination strategies to prevent or limit these infections as a rational approach to tackle these infections. In this review, immunization and immunotherapy approaches currently available and under study against these bacterial pathogens is reviewed. Ongoing active and passive immunization clinical trials against . infections is also reviewed. Novel identified bacterial targets and their possible exploitation for the development of immunization and immunotherapy strategies against . and . complex and infections are also presented and discussed.
PubMed: 34207253
DOI: 10.3390/vaccines9060670 -
Clinical Microbiology Reviews Jun 2020(formerly ) was once thought to be a single bacterial species but has expanded to the complex (Bcc), comprising 24 closely related opportunistic pathogenic species.... (Review)
Review
(formerly ) was once thought to be a single bacterial species but has expanded to the complex (Bcc), comprising 24 closely related opportunistic pathogenic species. These bacteria have a widespread environmental distribution, an extraordinary metabolic versatility, a complex genome with three chromosomes, and a high capacity for rapid mutation and adaptation. Additionally, they present an inherent resistance to antibiotics and antiseptics, as well as the abilities to survive under nutrient-limited conditions and to metabolize the organic matter present in oligotrophic aquatic environments, even using certain antimicrobials as carbon sources. These traits constitute the reason that Bcc bacteria are considered feared contaminants of aqueous pharmaceutical and personal care products and the frequent reason behind nonsterile product recalls. Contamination with Bcc has caused numerous nosocomial outbreaks in health care facilities, presenting a health threat, particularly for patients with cystic fibrosis and chronic granulomatous disease and for immunocompromised individuals. This review addresses the role of Bcc bacteria as a potential public health problem, the mechanisms behind their success as contaminants of pharmaceutical products, particularly in the presence of biocides, the difficulties encountered in their detection, and the preventive measures applied during manufacturing processes to control contamination with these objectionable microorganisms. A summary of Bcc-related outbreaks in different clinical settings, due to contamination of diverse types of pharmaceutical products, is provided.
Topics: Burkholderia Infections; Burkholderia cepacia complex; Cross Infection; Disease Outbreaks; Drug Contamination; Drug Resistance, Multiple, Bacterial; Humans; Opportunistic Infections; Water Microbiology
PubMed: 32295766
DOI: 10.1128/CMR.00139-19 -
Viruses Jul 2021The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all... (Review)
Review
The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all aspects of modern medicine. Particularly concerning, yet insufficiently addressed, are the members of the complex (Bcc), a group of at least twenty opportunistic, hospital-transmitted, and notoriously drug-resistant species, which infect and cause morbidity in patients who are immunocompromised and those afflicted with chronic illnesses, including cystic fibrosis (CF) and chronic granulomatous disease (CGD). One potential solution to the antimicrobial resistance crisis is phage therapy-the use of phages for the treatment of bacterial infections. Although phage therapy has a long and somewhat checkered history, an impressive volume of modern research has been amassed in the past decades to show that when applied through specific, scientifically supported treatment strategies, phage therapy is highly efficacious and is a promising avenue against drug-resistant and difficult-to-treat pathogens, such as the Bcc. In this review, we discuss the clinical significance of the Bcc, the advantages of phage therapy, and the theoretical and clinical advancements made in phage therapy in general over the past decades, and apply these concepts specifically to the nascent, but growing and rapidly developing, field of Bcc phage therapy.
Topics: Bacteriophages; Burkholderia cepacia complex; Humans; Phage Therapy
PubMed: 34372537
DOI: 10.3390/v13071331 -
Frontiers in Cellular and Infection... 2021The genus contains over 80 different Gram-negative species including both plant and human pathogens, the latter of which can be classified into one of two groups: the... (Review)
Review
The genus contains over 80 different Gram-negative species including both plant and human pathogens, the latter of which can be classified into one of two groups: the complex (Bpc) or the complex (Bcc). Bpc pathogens and are highly virulent, and both have considerable potential for use as Tier 1 bioterrorism agents; thus there is great interest in the development of novel vaccines and therapeutics for the prevention and treatment of these infections. While Bcc pathogens , , and are not considered bioterror threats, the incredible impact these infections have on the cystic fibrosis community inspires a similar demand for vaccines and therapeutics for the prevention and treatment of these infections as well. Understanding how these pathogens interact with and evade the host immune system will help uncover novel therapeutic targets within these organisms. Given the important role of the complement system in the clearance of bacterial pathogens, this arm of the immune response must be efficiently evaded for successful infection to occur. In this review, we will introduce the species to be discussed, followed by a summary of the complement system and known mechanisms by which pathogens interact with this critical system to evade clearance within the host. We will conclude with a review of literature relating to the interactions between the herein discussed species and the host complement system, with the goal of highlighting areas in this field that warrant further investigation.
Topics: Burkholderia; Burkholderia Infections; Burkholderia pseudomallei; Complement System Proteins; Humans; Immune Evasion; Melioidosis
PubMed: 34660335
DOI: 10.3389/fcimb.2021.701362 -
Frontiers in Immunology 2022Inflammatory caspases detect cytosol-invasive Gram-negative bacteria by monitoring for the presence of LPS in the cytosol. This should provide defense against the... (Review)
Review
Inflammatory caspases detect cytosol-invasive Gram-negative bacteria by monitoring for the presence of LPS in the cytosol. This should provide defense against the cytosol-invasive and species by lysing the infected cell pyroptosis. However, recent evidence has shown caspase-11 and gasdermin D activation can result in two different outcomes: pyroptosis and autophagy. complex has the ability invade the cytosol but is unable to inhibit caspase-11 and gasdermin D. Yet instead of activating pyroptosis during infection with these bacteria, the autophagy pathway is stimulated through caspases and gasdermin D. In contrast, can invade the cytosol where caspasae-11 and gasdermin D is activated but the result is pyroptosis of the infected cell. In this review we propose a hypothetical model to explain why autophagy would be the solution to kill one type of species, but another species is killed by pyroptosis. For pathogens with high virulence, pyroptosis is the only solution to kill bacteria. This explains why some pathogens, such as have evolved methods to inhibit caspase-11 and gasdermin D as well as autophagy. We also discuss similar regulatory steps that affect caspase-1 that may permit the cell to forbear undergoing pyroptosis after caspase-1 activates in response to bacteria with partially effective virulence factors.
Topics: Autophagy; Caspase 1; Caspases; Cytosol; Pyroptosis
PubMed: 35422805
DOI: 10.3389/fimmu.2022.871190 -
Annals of Medicine Dec 2024complex () is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic... (Review)
Review
complex () is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic fibrosis (CF), can cause severe lung infections that lead to accelerated lung damage, which can be complicated by necrotizing pneumonia accompanied by high fevers, leucocytosis, and bacteraemia, which commonly causes fatal outcomes. Specifically, infection by is considered an exclusion criterion for lung transplantation. The species of exhibit both genetic and phenotypic hypervariability that complicate their accurate microbiological identification. Automated methods such as MALDI-TOF can err in the determination of species. Their slow growth even in selective agars and the absence of international consensuses on the optimal conditions for their isolation make early diagnosis a difficult challenge to overcome. The absence of correlations between antibiograms and clinical results has resulted in the absence of standardized cut-off values of antimicrobial susceptibility, a fact that brings a latent risk since incorrect antibiotic therapy can induce the selection of more aggressive variants that worsen the clinical picture of the host, added to the absence of a clear therapeutic guide for the eradication of pulmonary infections by in patients with CF, resulting in frequently ineffective treatments. There is an urgent need to standardize methods and diagnostic tools that would allow an early and accurate diagnosis, as well as to perform clinical studies of the effectiveness of available antibiotics to eradicate infections, which would allow us to establish standardized therapeutic schemes for -infected patients.
Topics: Humans; Cystic Fibrosis; Burkholderia cepacia complex; Lung Transplantation; Anti-Bacterial Agents; Bacteremia
PubMed: 38261606
DOI: 10.1080/07853890.2024.2307503 -
Expert Opinion on Drug Discovery Jul 2021: The increasing threat of antibiotic-resistant pathogens makes it imperative that new antibiotics to combat them are discovered. is a genus of Gram-negative,... (Review)
Review
: The increasing threat of antibiotic-resistant pathogens makes it imperative that new antibiotics to combat them are discovered. is a genus of Gram-negative, non-sporulating bacteria. While ubiquitous and capable of growing within plants and groundwater, they are primarily soil-dwelling organisms. These include the more virulent forms of such as , and the complex (Bcc).: This review provides a synopsis of current research on the natural products isolated from the genus . The authors also cover the research on the drug discovery efforts that have been performed on the natural products derived from .: Though has a small number of pathogenic species, the majority of the genus is avirulent and almost all members of the genus are capable of producing useful antimicrobial products that could potentially lead to the development of novel therapeutics against infectious diseases. The need for discovery of new antibiotics is urgent due to the ever-increasing prevalence of antibiotic-resistant pathogens, coupled with the decline in the discovery of new antibiotics.
Topics: Biological Products; Burkholderia; Burkholderia Infections; Burkholderia pseudomallei; Drug Discovery; Humans
PubMed: 33467922
DOI: 10.1080/17460441.2021.1877655