-
Drug Resistance Updates : Reviews and... Sep 2016The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus... (Review)
Review
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Burkholderia; Burkholderia Infections; Burkholderia mallei; Burkholderia pseudomallei; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genes, MDR; Glanders; Horses; Humans; Melioidosis; Porins; Tetrahydrofolate Dehydrogenase
PubMed: 27620956
DOI: 10.1016/j.drup.2016.07.003 -
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 -
Annals of Clinical Microbiology and... Feb 2019Bacteria belonging to the Burkholderia cepacia complex (Bcc) are among the most important pathogens isolated from cystic fibrosis (CF) patients and in hospital acquired... (Review)
Review
Bacteria belonging to the Burkholderia cepacia complex (Bcc) are among the most important pathogens isolated from cystic fibrosis (CF) patients and in hospital acquired infections (HAI). Accurate identification of Bcc is questionable by conventional biochemical methods. Clonal typing of Burkholderia is also limited due to the problem with identification. Phenotypic identification methods such as VITEK2, protein signature identification methods like VITEK MS, Bruker Biotyper, and molecular targets such as 16S rRNA, recA, hisA and rpsU were reported with varying level of discrimination to identify Bcc. rpsU and/or 16S rRNA sequencing, VITEK2, VITEK MS and Bruker Biotyper could discriminate between Burkholderia spp. and non-Burkholderia spp. Whereas, Bcc complex level identification can be given by VITEK MS, Bruker Biotyper, and 16S rRNA/rpsU/recA/hisA sequencing. For species level identification within Bcc hisA or recA sequencing are reliable. Identification of Bcc is indispensable in CF patients and HAI to ensure appropriate antimicrobial therapy.
Topics: Bacterial Proteins; Bacterial Typing Techniques; Burkholderia Infections; Burkholderia cepacia complex; Cross Infection; Cystic Fibrosis; DNA, Bacterial; Humans; Molecular Typing; Phylogeny; RNA, Ribosomal, 16S; Rec A Recombinases; Sequence Analysis, DNA; Whole Genome Sequencing
PubMed: 30717798
DOI: 10.1186/s12941-019-0306-0 -
Vaccines Apr 2016Burkholderia comprises a wide variety of environmental Gram-negative bacteria. Burkholderia cepacia complex (Bcc) includes several Burkholderia species that pose a... (Review)
Review
Burkholderia comprises a wide variety of environmental Gram-negative bacteria. Burkholderia cepacia complex (Bcc) includes several Burkholderia species that pose a health hazard as they are able to cause respiratory infections in patients with chronic granulomatous disease and cystic fibrosis. Due to the intrinsic resistance to a wide array of antibiotics and naturally occurring immune evasion strategies, treatment of Bcc infections often proves to be unsuccessful. To date, limited work related to vaccine development has been performed for Bcc pathogens. In this review, we have gathered key aspects of Bcc research that have been reported in recent years related to vaccine efforts, virulence, immune responses, and animal models, and use this information to inform the research community of areas of opportunity toward development of a viable Bcc vaccine.
PubMed: 27092530
DOI: 10.3390/vaccines4020010 -
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 -
Pathogens and Disease Aug 2016The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of... (Review)
Review
The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them.
Topics: Adaptation, Biological; Animals; Burkholderia; Burkholderia Infections; Chronic Disease; Host-Pathogen Interactions; Humans; Immune System; Melioidosis; Virulence Factors
PubMed: 27440810
DOI: 10.1093/femspd/ftw070 -
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 -
Journal of Ophthalmic Inflammation and... Nov 2023To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis.
PURPOSE
To report the clinical characteristics, antibiotic susceptibilities, and review the literature of Burkholderia cepacia complex (BCC) associated endophthalmitis.
STUDY DESIGN
Retrospective, observational case series.
METHODS
Clinical and microbiology records were reviewed for patients evaluated at the Bascom Palmer Eye Institute and diagnosed wisth culture-confirmed endophthalmitis due to BCC. Antibiotic susceptibility profiles were generated using standard microbiologic protocols via an automated VITEK system.
RESULTS
Endophthalmitis associated with BCC was diagnosed in three patients. Infection occurred in the setting of post-penetrating keratoplasty (PKP), glaucoma filtering surgery, and suspected trauma. All isolates demonstrated in vitro susceptibility to ceftazidime and meropenem. Presenting visual acuity (VA) ranged from hand motion to light perception. Initial treatment strategies included intravitreal ceftazidime (2.25 mg/0.1 mL) and vancomycin (1.0 mg/0.1 mL) injections with fortified topical antibiotics in 2 patients, and surgical debridement of a corneoscleral melt with patch graft along with both topical fortified antibiotics oral antibiotics in the third patient. In all 3 patients, there was no VA improvement at last follow-up, as 2 eyes ultimately underwent enucleation and 1 eye exhibited phthisis bulbi at last follow-up. BCC related endophthalmitis was reviewed among 13 reports. Treatment outcomes were generally poor and antibiotic resistance was common. These BCC isolates cases demonstrated broad resistance patterns, with susceptibilities to ceftazidime (58%), ciprofloxacin (53%), and gentamicin (33%).
CONCLUSIONS
Endophthalmitis caused by B. cepacia is a rare clinical entity with generally poor visual outcomes despite prompt treatment with appropriate antibiotics.
PubMed: 37922028
DOI: 10.1186/s12348-023-00370-1 -
Frontiers in Cellular and Infection... 2017is a genus within the β that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur... (Review)
Review
is a genus within the β that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur within the genus. These include and , opportunistic pathogens that can infect the lungs of patients with cystic fibrosis, and are members of the complex (Bcc). is also an opportunistic pathogen, but in contrast to Bcc species it causes the tropical human disease melioidosis, while its close relative is the causative agent of glanders in horses. For these pathogens to survive within a host and cause disease they must be able to acquire iron. This chemical element is essential for nearly all living organisms due to its important role in many enzymes and metabolic processes. In the mammalian host, the amount of accessible free iron is negligible due to the low solubility of the metal ion in its higher oxidation state and the tight binding of this element by host proteins such as ferritin and lactoferrin. As with other pathogenic bacteria, species have evolved an array of iron acquisition mechanisms with which to capture iron from the host environment. These mechanisms include the production and utilization of siderophores and the possession of a haem uptake system. Here, we summarize the known mechanisms of iron acquisition in pathogenic species and discuss the evidence for their importance in the context of virulence and the establishment of infection in the host. We have also carried out an extensive bioinformatic analysis to identify which siderophores are produced by each species that is pathogenic to humans.
Topics: Animals; Burkholderia; Burkholderia Infections; Burkholderia gladioli; Burkholderia mallei; Burkholderia pseudomallei; Computational Biology; Cystic Fibrosis; Ferritins; Glanders; Heme; Horses; Humans; Iron; Lactoferrin; Lung; Melioidosis; Siderophores; Virulence
PubMed: 29164069
DOI: 10.3389/fcimb.2017.00460