Cangene Gold Medal Award Lecture — Genomic analysis and modification ofBurkholderia cepaciacomplex bacteriophages1This article is based on a presentation by Dr. Karlene Lynch at the 61st Annual Meeting of the Canadian Society of Microbiologists in St. John’s, Newfoundland and Labrador, on 21 June 2011. Dr. Lynch was the recipient of the 2011 Cangene Gold Medal as the Canadian Graduate Student Microbiologist of the Year, an annual award sponsored by Cangene Corporation intended to recognize excellence in graduate research.

2012 ◽  
Vol 58 (3) ◽  
pp. 221-235 ◽  
Author(s):  
Karlene H. Lynch ◽  
Jonathan J. Dennis
Keyword(s):  
Newfoundland And Labrador ◽  
Burkholderia Cepacia ◽  
Phage Therapy ◽  
Opportunistic Infections ◽  
Bacterial Species ◽  
Genomic Analysis ◽  
Gold Medal ◽  
Burkholderia Cepacia Complex ◽  
Bacterial Gene ◽  
Therapy Strategy

The Burkholderia cepacia complex (Bcc) is a group of 17 Gram-negative predominantly environmental bacterial species that cause potentially fatal opportunistic infections in cystic fibrosis (CF) patients. Although its prevalence in these individuals is lower than that of Staphylococcus aureus and Pseudomonas aeruginosa , the Bcc remains a serious problem in the CF community because of the pathogenicity, transmissibility, and inherent antibiotic resistance of these organisms. An alternative treatment for Bcc infections that is currently being developed is phage therapy, the clinical use of viruses that infect bacteria. To assess the suitability of individual phage isolates for therapeutic use, the complete genome sequences of a panel of Bcc‐specific phages were determined and analyzed. These sequences encode a broad range of proteins with a gradient of relatedness to phage and bacterial gene products from Burkholderia and other genera. The majority of these phages were found not to encode virulence factors, and despite their predominantly temperate nature, a proof-of-principle experiment has shown that they may be modified to a lytic form. Both the genomic characterization and subsequent engineering of Bcc‐specific phages are fundamental to the development of an effective phage therapy strategy for these bacteria.

scholarly journals Comparison of Microbiological Characteristics and Genetic Diversity between Burkholderia cepacia Complex Isolates from Vascular Access and Other Clinical Infections

2020 ◽  
Vol 9 (1) ◽  
pp. 51
Author(s):  
Min Yi Wong ◽  
Yuan-Hsi Tseng ◽  
Tsung-Yu Huang ◽  
Bor-Shyh Lin ◽  
Chun-Wu Tung ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Vascular Access ◽  
Burkholderia Cepacia ◽  
Bacterial Species ◽  
Diversity Indices ◽  
Burkholderia Cepacia Complex ◽  
Reca Gene ◽  
Clinical Effects ◽  
Environmental Distribution ◽  
Microbiological Characteristics

Burkholderia cepacia complex (BCC) is a group of closely related bacteria with widespread environmental distribution. BCC bacteria are opportunistic pathogens that cause nosocomial infections in patients, especially cystic fibrosis (CF). Multilocus sequence typing (MLST) is used nowadays to differentiate species within the BCC complex. This study collected 41 BCC isolates from vascular access infections (VAIs) and other clinical infections between 2014 and 2020. We preliminarily identified bacterial isolates using standard biochemical procedures and further conducted recA gene sequencing and MLST for species identification. We determined genetic diversity indices using bioinformatics software. We studied 14 isolates retrieved from patients with VAIs and observed that Burkholderia cepacia was the predominant bacterial species, and B. contaminans followed by B. cenocepacia were mainly retrieved from patients with other infections. According to MLST data, we identified that all B. contaminans isolates belonged to ST102, while a wide variety of sequence types (STs) were found in B. cenocepacia isolates. In summary, the high diversity and easy transmission of BCC increase BCC infections, which provides insights into their potential clinical effects in non-CF infections.

scholarly journals Burkholderia cepacia Complex Bacteria: a Feared Contamination Risk in Water-Based Pharmaceutical Products

2020 ◽  
Vol 33 (3) ◽  
Author(s):  
Mariana Tavares ◽  
Mariya Kozak ◽  
Alexandra Balola ◽  
Isabel Sá-Correia
Keyword(s):  
Burkholderia Cepacia ◽  
Bacterial Species ◽  
Public Health Problem ◽  
Pharmaceutical Products ◽  
Health Care Facilities ◽  
Burkholderia Cepacia Complex ◽  
Pseudomonas Cepacia ◽  
Environmental Distribution ◽  
Content Type ◽  
Metabolic Versatility

SUMMARY Burkholderia cepacia (formerly Pseudomonas cepacia) was once thought to be a single bacterial species but has expanded to the Burkholderia cepacia 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.

scholarly journals Aerosol Phage Therapy Efficacy in Burkholderia cepacia Complex Respiratory Infections

2014 ◽  
Vol 58 (7) ◽  
pp. 4005-4013 ◽  
Author(s):  
Diana D. Semler ◽  
Amanda D. Goudie ◽  
Warren H. Finlay ◽  
Jonathan J. Dennis
Keyword(s):  
Intraperitoneal Injection ◽  
Burkholderia Cepacia ◽  
Phage Therapy ◽  
Respiratory Infections ◽  
Burkholderia Cepacia Complex ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Therapy Efficacy

ABSTRACTPhage therapy has been suggested as a potential treatment for highly antibiotic-resistant bacteria, such as the species of theBurkholderia cepaciacomplex (BCC). To address this hypothesis, experimentalB. cenocepaciarespiratory infections were established in mice using a nebulizer and a nose-only inhalation device. Following infection, the mice were treated with one of fiveB. cenocepacia-specific phages delivered as either an aerosol or intraperitoneal injection. The bacterial and phage titers within the lungs were assayed 2 days after treatment, and mice that received the aerosolized phage therapy demonstrated significant decreases in bacterial loads. Differences in phage activity were observedin vivo. Mice that received phage treatment by intraperitoneal injection did not demonstrate significantly reduced bacterial loads, although phage particles were isolated from their lung tissue. Based on these data, aerosol phage therapy appears to be an effective method for treating highly antibiotic-resistant bacterial respiratory infections, including those caused by BCC bacteria.

scholarly journals Experimental Bacteriophage Therapy Increases Survival of Galleria mellonella Larvae Infected with Clinically Relevant Strains of the Burkholderia cepacia Complex

2009 ◽  
Vol 53 (5) ◽  
pp. 2205-2208 ◽  
Author(s):  
Kimberley D. Seed ◽  
Jonathan J. Dennis
Keyword(s):  
Alternative Treatment ◽  
Burkholderia Cepacia ◽  
Phage Therapy ◽  
Galleria Mellonella ◽  
Respiratory Infections ◽  
Burkholderia Cepacia Complex ◽  
Infection Model ◽  
Bacteriophage Therapy ◽  
Antibiotic Resistant

ABSTRACT The Burkholderia cepacia complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages of the BCC have been isolated and characterized, no studies have yet examined phage therapy against the BCC in vivo. In a caterpillar infection model, we show that BCC phage therapy is an alternative treatment possibility and is highly effective under specific conditions.

scholarly journals Current Advances in Burkholderia Vaccines Development

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2671
Author(s):  
Guanbo Wang ◽  
Paulina Zarodkiewicz ◽  
Miguel A. Valvano
Keyword(s):  
Burkholderia Cepacia ◽  
Burkholderia Pseudomallei ◽  
Vaccine Development ◽  
Respiratory Infections ◽  
Bacterial Species ◽  
Antimicrobial Treatment ◽  
Burkholderia Cepacia Complex ◽  
Attractive Alternative ◽  
Wide Range ◽  
Substantial Progress

The genus Burkholderia includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are Burkholderia mallei, Burkholderia pseudomallei, and the members of the Burkholderia cepacia complex (Bcc). B. mallei and B. pseudomallei, the cause of glanders and melioidosis, respectively, are considered potential bioweapons. The Bcc comprises a subset of Burkholderia species associated with respiratory infections in people with chronic granulomatous disease and cystic fibrosis. Antimicrobial treatment of Burkholderia 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 Burkholderia infections are still unavailable, substantial progress has been made over recent years in the development of vaccines against B. pseudomallei and B. mallei. This review critically discusses the current advances in vaccine development against B. mallei, B. pseudomallei, and the Bcc.

scholarly journals Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1331
Author(s):  
Philip Lauman ◽  
Jonathan J. Dennis
Keyword(s):  
Burkholderia Cepacia ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Burkholderia Cepacia Complex ◽  
Drug Resistant ◽  
The Past ◽  
Resistant Species

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 Burkholderia cepacia 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.

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