Case Report: Chronic Bacterial Prostatitis Treated With Phage Therapy After Multiple Failed Antibiotic Treatments

Background: Chronic Bacterial Prostatitis (CBP) is an inflammatory condition caused by a persistent bacterial infection of the prostate gland and its surrounding areas in the male pelvic region. It is most common in men under 50 years of age. It is a long-lasting and debilitating condition that severely deteriorates the patient’s quality of life. Anatomical limitations and antimicrobial resistance limit the effectiveness of antibiotic treatment of CBP. Bacteriophage therapy is proposed as a promising alternative treatment of CBP and related infections. Bacteriophage therapy is the use of lytic bacterial viruses to treat bacterial infections. Many cases of CBP are complicated by infections caused by both nosocomial and community acquired multidrug resistant bacteria. Frequently encountered strains include Vancomycin resistant Enterococci, Extended Spectrum Beta Lactam resistant Escherichia coli, other gram-positive organisms such as Staphylococcus and Streptococcus, Enterobacteriaceae such as Klebsiella and Proteus, and Pseudomonas aeruginosa, among others.Case Presentation: We present a patient with the typical manifestations of CBP. The patient underwent multiple courses of antibiotic treatment without any long-term resolution of his symptoms. Testing of prostatic secretion and semen samples revealed pathogenic bacteria in each case, which collectively included members of the Staphylococcal species such as Methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus haemolyticus, Enterococcus faecalis, and Streptococcus mitis, among others.Methods and Outcome: Bacteriophage preparations from the Eliava Institute were used to treat the patient after establishing phage sensitivity to the pathogenic bacteria. Significant improvements in symptoms and re-testing of samples after bacteriophage treatment indicated a reduction in the bacterial load and resolution of the infection.Discussion: The patient saw significant improvement of symptoms, and positive dynamics in bacterial titers and ultrasound controls after phage therapy. The failure of antibiotic therapy and subsequent success of bacteriophage therapy in treating chronic bacterial prostatitis shows the effectiveness of bacteriophages in controlling chronic infections in areas of low vascularity and anatomical complexity. These cases also highlight the efficacy of phages in overcoming antibiotic-resistant infections as well as biofilm infections.

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Determination of the optimal bacteriophage dose to control Pseudomonas aeruginosa using evolutionary programming and stochastic kinetics

10.7287/peerj.preprints.2359v1 ◽

2016 ◽

Author(s):

Diana C Ardila ◽

Juan D Castro ◽

Angela V Holguín ◽

Viviana Clavijo ◽

Catalina Prada ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Reverse Engineering ◽

Pathogenic Bacteria ◽

Phage Therapy ◽

Evolutionary Programming ◽

Stochastic Simulations ◽

Resistant Bacteria ◽

Multiple Drug ◽

Promising Alternative

Phage-therapy is a promising alternative against pathogenic, multiple drug resistant bacteria. In this work we propose an algorithm to determine the optimal bacteriophage dose able to minimize a population of Pseudomonas aeruginosa. Reverse engineering was used to determine the kinetic parameters; subsequently, a bi-level optimization platform was implemented for a model based on evolutionary programming. Our prediction of optimal dose was tested in vitro with planktonic cultures of P. aeruginosa. From the data obtained, we conclude that reverse engineering and stochastic simulations are a useful approach to find optimal phage doses against pathogenic bacteria, an important step for the implementation of phage-therapy.

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Determination of the optimal bacteriophage dose to control Pseudomonas aeruginosa using evolutionary programming and stochastic kinetics

10.7287/peerj.preprints.2359 ◽

2016 ◽

Author(s):

Diana C Ardila ◽

Juan D Castro ◽

Angela V Holguín ◽

Viviana Clavijo ◽

Catalina Prada ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Reverse Engineering ◽

Pathogenic Bacteria ◽

Phage Therapy ◽

Evolutionary Programming ◽

Stochastic Simulations ◽

Resistant Bacteria ◽

Multiple Drug ◽

Promising Alternative

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How to Train Your Phage: The Recent Efforts in Phage Training

Biologics ◽

10.3390/biologics1020005 ◽

2021 ◽

Vol 1 (2) ◽

pp. 70-88

Author(s):

Abdallah Abdelsattar ◽

Alyaa Dawooud ◽

Nouran Rezk ◽

Salsabil Makky ◽

Anan Safwat ◽

...

Keyword(s):

Host Range ◽

Pathogenic Bacteria ◽

Bacterial Resistance ◽

Phage Therapy ◽

Current Knowledge ◽

Lytic Replication ◽

Resistant Bacteria ◽

Infection Cycles ◽

Different Strains ◽

Specific Species

Control of pathogenic bacteria by deliberate application of predatory phages has potential as a powerful therapy against antibiotic-resistant bacteria. The key advantages of phage biocontrol over antibacterial chemotherapy are: (1) an ability to self-propagate inside host bacteria, (2) targeted predation of specific species or strains of bacteria, (3) adaptive molecular machinery to overcome resistance in target bacteria. However, realizing the potential of phage biocontrol is dependent on harnessing or adapting these responses, as many phage species switch between lytic infection cycles (resulting in lysis) and lysogenic infection cycles (resulting in genomic integration) that increase the likelihood of survival of the phage in response to external stress or host depletion. Similarly, host range will need to be optimized to make phage therapy medically viable whilst avoiding the potential for deleteriously disturbing the commensal microbiota. Phage training is a new approach to produce efficient phages by capitalizing on the evolved response of wild-type phages to bacterial resistance. Here we will review recent studies reporting successful trials of training different strains of phages to switch into lytic replication mode, overcome bacterial resistance, and increase their host range. This review will also highlight the current knowledge of phage training and future implications in phage applications and phage therapy and summarize the recent pipeline of the magistral preparation to produce a customized phage for clinical trials and medical applications.

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Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0030 ◽

2017 ◽

Vol 63 (11) ◽

pp. 865-879 ◽

Cited By ~ 26

Author(s):

Ayman El-Shibiny ◽

Salma El-Sahhar

Keyword(s):

Bacterial Infections ◽

Pathogenic Bacteria ◽

Phage Therapy ◽

Multidrug Resistant ◽

Clinical Applications ◽

Western World ◽

Resistant Bacteria ◽

Vaccine Production ◽

Bacterial Populations ◽

Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

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374 PATHOGEN ERADICATION BY PHAGE THERAPY IN PATIENTS WITH CHRONIC BACTERIAL PROSTATITIS

European Urology Supplements ◽

10.1016/s1569-9056(10)60372-7 ◽

2010 ◽

Vol 9 (2) ◽

pp. 140 ◽

Cited By ~ 4

Author(s):

S. Letkiewicz ◽

R. Międzvbrodzki ◽

M. Kłak ◽

B. Weber Dąbrowska ◽

A. Górski

Keyword(s):

Phage Therapy ◽

Chronic Bacterial Prostatitis ◽

Bacterial Prostatitis

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The Concerted Action of Two B3-Like Prophage Genes Excludes Superinfecting Bacteriophages by Blocking DNA Entry into Pseudomonas aeruginosa

Journal of Virology ◽

10.1128/jvi.00953-20 ◽

2020 ◽

Vol 94 (15) ◽

Author(s):

Marco Antonio Carballo-Ontiveros ◽

Adrián Cazares ◽

Pablo Vinuesa ◽

Luis Kameyama ◽

Gabriel Guarneros

Keyword(s):

Pseudomonas Aeruginosa ◽

Pathogenic Bacteria ◽

Phage Therapy ◽

Alternative Therapy ◽

Multidrug Resistant ◽

Open Reading Frames ◽

Resistant Bacteria ◽

Content Type ◽

Secondary Infections ◽

Genes Encoding

ABSTRACT In this study, we describe seven vegetative phage genomes homologous to the historic phage B3 that infect Pseudomonas aeruginosa. Like other phage groups, the B3-like group contains conserved (core) and variable (accessory) open reading frames (ORFs) grouped at fixed regions in their genomes; however, in either case, many ORFs remain without assigned functions. We constructed lysogens of the seven B3-like phages in strain Ps33 of P. aeruginosa, a novel clinical isolate, and assayed the exclusion phenotype against a variety of temperate and virulent superinfecting phages. In addition to the classic exclusion conferred by the phage immunity repressor, the phenotype observed in B3-like lysogens suggested the presence of other exclusion genes. We set out to identify the genes responsible for this exclusion phenotype. Phage Ps56 was chosen as the study subject since it excluded numerous temperate and virulent phages. Restriction of the Ps56 genome, cloning of several fragments, and resection of the fragments that retained the exclusion phenotype allowed us to identify two core ORFs, so far without any assigned function, as responsible for a type of exclusion. Neither gene expressed separately from plasmids showed activity, but the concurrent expression of both ORFs is needed for exclusion. Our data suggest that phage adsorption occurs but that phage genome translocation to the host’s cytoplasm is defective. To our knowledge, this is the first report on this type of exclusion mediated by a prophage in P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is a Gram-negative bacterium frequently isolated from infected immunocompromised patients, and the strains are resistant to a broad spectrum of antibiotics. Recently, the use of phages has been proposed as an alternative therapy against multidrug-resistant bacteria. However, this approach may present various hurdles. This work addresses the problem that pathogenic bacteria may be lysogenized by phages carrying genes encoding resistance against secondary infections, such as those used in phage therapy. Discovering phage genes that exclude superinfecting phages not only assigns novel functions to orphan genes in databases but also provides insight into selection of the proper phages for use in phage therapy.

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Mycobacterium phage Butters-encoded proteins contribute to host defense against viral attack

10.1101/2020.04.27.053744 ◽

2020 ◽

Author(s):

Catherine M. Mageeney ◽

Hamidu T. Mohammed ◽

Marta Dies ◽

Samira Anbari ◽

Netta Cudkevich ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Phage Therapy ◽

Defense Mechanism ◽

Resistant Bacteria ◽

Two Component System ◽

Bacterial Genomes ◽

Bacterial Host ◽

Bioinformatics Analyses ◽

Defense Systems ◽

Two Component

ABSTRACTA diverse set of prophage-mediated mechanisms protecting bacterial hosts from infection has been recently uncovered within Cluster N mycobacteriophages. In that context, we unveil a novel defense mechanism in Cluster N prophage Butters. By using bioinformatics analyses, phage plating efficiency experiments, microscopy, and immunoprecipitation assays, we show that Butters genes located in the central region of the genome play a key role in the defense against heterotypic viral attack. Our study suggests that a two component system articulated by interactions between protein products of genes 30 and 31 confers defense against heterotypic phage infection by PurpleHaze or Alma, but is insufficient to confer defense against attack by the heterotypic phage Island3. Therefore, based on heterotypic phage plating efficiencies on the Butters lysogen, additional prophage genes required for defense are implicated.IMPORTANCEMany sequenced bacterial genomes including pathogenic bacteria contain prophages. Some prophages encode defense systems that protect their bacterial host against heterotypic viral attack. Understanding the mechanisms undergirding these defense systems will be critical to development of phage therapy that circumvents these defenses. Additionally, such knowledge will help engineer phage-resistant bacteria of industrial importance.

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Bacteriophage therapy: experience from the Eliava Institute, Georgia

Microbiology Australia ◽

10.1071/ma08096 ◽

2008 ◽

Vol 29 (2) ◽

pp. 96 ◽

Cited By ~ 8

Author(s):

Nina Chanishvili ◽

Richard Sharp

Keyword(s):

Soviet Union ◽

Former Soviet Union ◽

Bacterial Infections ◽

Phage Therapy ◽

Effective Means ◽

Resistant Bacteria ◽

Bacteriophage Therapy ◽

Antibiotic Resistant ◽

Bacterial Diseases ◽

Wide Range

The lysis of bacteria by bacteriophage was independently discovered by Frederick Twort and Felix d?Herelle but it was d?Herelle who proposed that bacteriophage might be applied to the control of bacterial diseases. Within the former Soviet Union (FSU), bacteriophage therapy was researched and applied extensively for the treatment of a wide range of bacterial infections. In the West, however, it was not explored with the same enthusiasm and was eventually discarded with the arrival of antibiotics. However, the increase in the incidence of multi-antibiotic-resistant bacteria and the absence of effective means for their control has led to increasing international interest in phage therapy and in the long experience of the Eliava Institute. The Eliava Institute of Bacteriophage, Microbiology and Virology (IBMV), which celebrates its 85th anniversary in 2008, was founded in Tbilisi in 1923 through the joint efforts of d?Herelle and the Georgian microbiologist, George Eliava.

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