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1.
Virology ; 548: 160-167, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32838937

RESUMO

Filamentous Inoviridae phages integrate into the chromosome of plant pathogens Xanthomonas as prophages, but their diversity and integrative mechanism are not completely understood. A proviral Cf2 sequence of 6454 bases from Xanthomonas citri genome was revived as infectious virions able to lysogenize its host. Unlike other Xanthomonas phages (Cf1c, φLf, Xf109, XacF1), Cf2 phage has RstA/RstB replication protein, and its attP has XerD binding arm and dif central region but lacks XerC binding arm. XerC+/Xf109 and XerD+/Cf2 attPs are in the opposite direction in phage genomes. Moreover, XerCD binding and XerD catalysis for strand exchange are necessary for site-specific integration of XerD+/Cf2 and XerC+/Xf109 attPs. Taken together, these results provide a new insight into the mechanism of XerCD-mediated recombination at XerD + attP.


Assuntos
Proteínas de Bactérias/metabolismo , Bacteriófagos/fisiologia , Inovirus/fisiologia , Integrases/metabolismo , Xanthomonas/enzimologia , Xanthomonas/virologia , Sítios de Ligação Microbiológicos , Proteínas de Bactérias/genética , Bacteriófagos/genética , Genoma Bacteriano , Inovirus/genética , Integrases/genética , Lisogenia , Integração Viral , Xanthomonas/genética
4.
Proc Natl Acad Sci U S A ; 117(34): 20576-20585, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32788352

RESUMO

Temperate bacteriophages can enter one of two life cycles following infection of a sensitive host: the lysogenic or the lytic life cycle. The choice between the two alternative life cycles is dependent upon a tight regulation of promoters and their cognate regulatory proteins within the phage genome. We investigated the genetic switch of TP901-1, a bacteriophage of Lactococcus lactis, controlled by the CI repressor and the modulator of repression (MOR) antirepressor and their interactions with DNA. We determined the solution structure of MOR, and we solved the crystal structure of MOR in complex with the N-terminal domain of CI, revealing the structural basis of MOR inhibition of CI binding to the DNA operator sites. 15N NMR Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion and rotating frame R 1ρ measurements demonstrate that MOR displays molecular recognition dynamics on two different time scales involving a repacking of aromatic residues at the interface with CI. Mutations in the CI:MOR binding interface impair complex formation in vitro, and when introduced in vivo, the bacteriophage switch is unable to choose the lytic life cycle showing that the CI:MOR complex is essential for proper functioning of the genetic switch. On the basis of sequence alignments, we show that the structural features of the MOR:CI complex are likely conserved among a larger family of bacteriophages from human pathogens implicated in transfer of antibiotic resistance.


Assuntos
Bacteriófagos/fisiologia , Lisogenia , Proteínas Repressoras/fisiologia , Proteínas Virais Reguladoras e Acessórias/fisiologia , Genoma Bacteriano , Interações Hospedeiro-Patógeno , Cinética , Lactococcus lactis/virologia , Simulação de Dinâmica Molecular , Regiões Operadoras Genéticas , Conformação Proteica , Proteínas Repressoras/química , Proteínas Virais Reguladoras e Acessórias/química
5.
J Med Microbiol ; 69(9): 1151-1168, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32840477

RESUMO

Introduction. Enterococcus faecalis is a facultative, anaerobic, opportunistic pathogen associated with medical and dental diseases. Bacterial phenotypic traits and pathogenesis are often influenced by lysogeny.Aim. The aim of this study was to characterize both the morphology and complete genome sequences of induced prophages purified from E. faecalis clinical isolates.Methodology. E. faecalis isolates were recovered from the roots of teeth of patients attending an endodontic clinic. The morphological features of isolated phage were characterized using transmission electron microscopy (TEM). DNA sequencing was performed using the Illumina MiSeq platform.Results. TEM indicated that the isolated φEf-vB1 prophage belongs to the family Siphoviridae. The φEf-vB1 prophage was stable over a wide range of temperatures and pH. Sequencing of φEf-vB1 DNA revealed that the phage genome is 37 561 bp in length with a G+C content of 37.6mol% and contained 53 ORFs. Comparison with previously predicted prophage genomes using blast revealed that φEf-vB1 has a high sequence similarity to previously characterized phage genomes. The lysogenic E. faecalis strain exhibited a higher biofilm formation capacity relative to the non-lysogenic strain.Conclusion. The current findings highlight the role of lysogeny in modification of E. faecalis properties and reveal the potential importance of prophages in E. faecalis biology and pathogenesis.


Assuntos
Bacteriófagos/fisiologia , Enterococcus faecalis/fisiologia , Enterococcus faecalis/virologia , Prófagos/fisiologia , Siphoviridae/isolamento & purificação , Composição de Bases , Cavidade Pulpar/microbiologia , Enterococcus faecalis/genética , Enterococcus faecalis/isolamento & purificação , Genoma Viral , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Lisogenia , Fases de Leitura Aberta , Periodontite , Prófagos/classificação , Prófagos/genética , Prófagos/isolamento & purificação , Siphoviridae/classificação , Siphoviridae/genética , Siphoviridae/fisiologia
6.
Nat Commun ; 11(1): 3748, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32719311

RESUMO

Flagellotropic bacteriophages engage flagella to reach the bacterial surface as an effective means to increase the capture radius for predation. Structural details of these viruses are of great interest given the substantial drag forces and torques they face when moving down the spinning flagellum. We show that the main capsid and auxiliary proteins form two nested chainmails that ensure the integrity of the bacteriophage head. Core stabilising structures are conserved in herpesviruses suggesting their ancestral origin. The structure of the tail also reveals a robust yet pliable assembly. Hexameric rings of the tail-tube protein are braced by the N-terminus and a ß-hairpin loop, and interconnected along the tail by the splayed ß-hairpins. By contrast, we show that the ß-hairpin has an inhibitory role in the tail-tube precursor, preventing uncontrolled self-assembly. Dyads of acidic residues inside the tail-tube present regularly-spaced motifs well suited to DNA translocation into bacteria through the tail.


Assuntos
Bacteriófagos/fisiologia , Flagelos/fisiologia , Motivos de Aminoácidos , Bacteriófagos/ultraestrutura , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , DNA/genética , DNA Viral/genética , Flagelos/ultraestrutura , Herpesviridae/ultraestrutura , Multimerização Proteica , Estrutura Secundária de Proteína , Vírion/ultraestrutura , Vitrificação
8.
Nat Protoc ; 15(9): 2867-2890, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32709990

RESUMO

The world is on the cusp of a post-antibiotic era, but researchers and medical doctors have found a way forward-by looking back at how infections were treated before the advent of antibiotics, namely using phage therapy. Although bacteriophages (phages) continue to lack drug approval in Western medicine, an increasing number of patients are being treated on an expanded-access emergency investigational new drug basis. To streamline the production of high-quality and clinically safe phage preparations, we developed a systematic procedure for medicinal phage isolation, liter-scale cultivation, concentration and purification. The 16- to 21-day procedure described in this protocol uses a combination of modified classic techniques, modern membrane filtration processes and no organic solvents to yield on average 23 mL of 1011 plaque-forming units (PFUs) per milliliter for Pseudomonas, Klebsiella, and Serratia phages tested. Thus, a single production run can produce up to 64,000 treatment doses at 109 PFUs, which would be sufficient for most expanded-access phage therapy cases and potentially for clinical phase I/II applications. The protocol focuses on removing endotoxins early by conducting multiple low-speed centrifugations, microfiltration, and cross-flow ultrafiltration, which reduced endotoxins by up to 106-fold in phage preparations. Implementation of a standardized phage cultivation and purification across research laboratories participating in phage production for expanded-access phage therapy might be pivotal to reintroduce phage therapy to Western medicine.


Assuntos
Bacteriófagos/crescimento & desenvolvimento , Bacteriófagos/isolamento & purificação , Técnicas de Cultura/normas , Terapia por Fagos , Bacteriófagos/química , Bacteriófagos/fisiologia , Medicina de Precisão , Controle de Qualidade , Padrões de Referência , Proteínas Virais/análise
9.
Nat Commun ; 11(1): 3034, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541663

RESUMO

Alphaproteobacteria, which are the most abundant microorganisms of temperate oceans, produce phage-like particles called gene transfer agents (GTAs) that mediate lateral gene exchange. However, the mechanism by which GTAs deliver DNA into cells is unknown. Here we present the structure of the GTA of Rhodobacter capsulatus (RcGTA) and describe the conformational changes required for its DNA ejection. The structure of RcGTA resembles that of a tailed phage, but it has an oblate head shortened in the direction of the tail axis, which limits its packaging capacity to less than 4,500 base pairs of linear double-stranded DNA. The tail channel of RcGTA contains a trimer of proteins that possess features of both tape measure proteins of long-tailed phages from the family Siphoviridae and tail needle proteins of short-tailed phages from the family Podoviridae. The opening of a constriction within the RcGTA baseplate enables the ejection of DNA into bacterial periplasm.


Assuntos
Bacteriófagos/fisiologia , Técnicas de Transferência de Genes , Rhodobacter capsulatus/genética , Rhodobacter capsulatus/virologia , Siphoviridae/fisiologia , Bacteriófagos/genética , Bacteriófagos/ultraestrutura , Microscopia Crioeletrônica , DNA Bacteriano/genética , Regulação Bacteriana da Expressão Gênica , Transferência Genética Horizontal , Siphoviridae/genética , Siphoviridae/ultraestrutura
10.
J Vis Exp ; (159)2020 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-32510504

RESUMO

Swarming is a form of surface motility observed in many bacterial species including Pseudomonas aeruginosa and Escherichia coli. Here, dense populations of bacteria move over large distances in characteristic tendril-shaped communities over the course of hours. Swarming is sensitive to several factors including medium moisture, humidity, and nutrient content. In addition, the collective stress response, which is observed in P. aeruginosa that are stressed by antibiotics or bacteriophage (phage), repels swarms from approaching the area containing the stress. The methods described here address how to control the critical factors that affect swarming. We introduce a simple method to monitor swarming dynamics and the collective stress response with high temporal resolution using a flatbed document scanner, and describe how to compile and perform a quantitative analysis of swarms. This simple and cost-effective method provides precise and well-controlled quantification of swarming and may be extended to other types of plate-based growth assays and bacterial species.


Assuntos
Pseudomonas aeruginosa/fisiologia , Estresse Fisiológico , Imagem com Lapso de Tempo , Antibacterianos/farmacologia , Bacteriófagos/fisiologia , Análise Custo-Benefício , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/virologia , Imagem com Lapso de Tempo/economia
11.
J Vis Exp ; (159)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32478753

RESUMO

Antimicrobial resistance, a major consequence of diagnostic uncertainty and antimicrobial overprescription, is an increasingly recognized cause of severe infections, complications, and mortality worldwide with a huge impact on our society and on the health system. In particular, patients with compromised immune systems or pre-existing and chronic pathologies, such as cystic fibrosis (CF), are subjected to frequent antibiotic treatments to control the infections with the appearance and diffusion of multidrug resistant isolates. Therefore, there is an urgent need to address alternative therapies to counteract bacterial infections. Use of bacteriophages, the natural enemies of bacteria, can be a possible solution. The protocol detailed in this work describes the application of phage therapy against Pseudomonas aeruginosa infection in CF zebrafish embryos. Zebrafish embryos were infected with P. aeruginosa to demonstrate that phage therapy is effective against P. aeruginosa infections as it reduces lethality, bacterial burden and pro-inflammatory immune response in CF embryos.


Assuntos
Fibrose Cística/microbiologia , Fibrose Cística/terapia , Embrião não Mamífero/microbiologia , Terapia por Fagos , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa/fisiologia , Peixe-Zebra/embriologia , Peixe-Zebra/microbiologia , Animais , Antibacterianos/farmacologia , Bacteriófagos/fisiologia , Citocinas/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Proteínas de Fluorescência Verde/metabolismo , Mediadores da Inflamação/metabolismo , Microinjeções , Morfolinos/farmacologia , Terapia por Fagos/efeitos adversos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Reprodutibilidade dos Testes
13.
Arch Virol ; 165(7): 1675-1678, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356184

RESUMO

Aeromonas hydrophila is an important finfish pathogen, besides being an opportunistic human pathogen. In the present study, the genomes of three A. hydrophila-specific phages, CF8, PS1, and PS2, were isolated, characterized and sequenced. Transmission electron microscopy showed that all three phages had typical Myoviridae morphology. The linear dsDNA genomes of CF8, PS1, and PS2 were 238,150 bp, 237,367 bp, and 240,447 bp in length, with a GC content of 42.2%, 38.8%, and 38.8%, respectively. The low sequence similarity (67.6% - 69.8% identity with 27.0% - 29.0% query coverage) to other phage genomes in the NCBI database indicated the novel nature of the CF8, PS1, and PS2 genomes. A total of 244, 247, and 250 open reading frames (ORFs) were predicted in the CF8, PS1, and PS2 genome, respectively. During the annotation process, functional predictions were made for 28-31 ORFs, while the rest were classified as "hypothetical proteins" with yet unknown functions. Genes for tRNAs were also detected in all phage genomes. As all three phages in the present study had a very narrow host range with lytic activity against only one strain of A. hydrophila, these phages could be good candidates for phage typing applications. Moreover, the endolysin- and lytic-transglycosylase-encoding genes could be used for recombinant cloning and expression of anti-microbial proteins.


Assuntos
Aeromonas hydrophila/virologia , Bacteriófagos/genética , Genoma Viral , Myoviridae/genética , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Composição de Bases , Sequência de Bases , Especificidade de Hospedeiro , Myoviridae/classificação , Myoviridae/isolamento & purificação , Myoviridae/fisiologia , Fases de Leitura Aberta , Filogenia
14.
Nat Microbiol ; 5(7): 917-928, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32251370

RESUMO

Bacteria have evolved diverse mechanisms to fend off predation by bacteriophages. We previously identified the Dnd system, which uses DndABCDE to insert sulfur into the DNA backbone as a double-stranded phosphorothioate (PT) modification, and DndFGH, a restriction component. Here, we describe an unusual SspABCD-SspE PT system in Vibrio cyclitrophicus, Escherichia coli and Streptomyces yokosukanensis, which has distinct genetic organization, biochemical functions and phenotypic behaviour. SspABCD confers single-stranded and high-frequency PTs with SspB acting as a nickase and possibly introducing nicks to facilitate sulfur incorporation. Strikingly, SspABCD coupled with SspE provides protection against phages in unusual ways: (1) SspE senses sequence-specific PTs by virtue of its PT-stimulated NTPase activity to exert its anti-phage activity, and (2) SspE inhibits phage propagation by introducing nicking damage to impair phage DNA replication. These results not only expand our knowledge about the diversity and functions of DNA PT modification but also enhance our understanding of the known arsenal of defence systems.


Assuntos
Bacteriófagos/fisiologia , Interações Hospedeiro-Patógeno , Fosfatos/metabolismo , Streptomyces/fisiologia , Streptomyces/virologia , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Sítios de Ligação , Ativação Enzimática , Genoma Bacteriano , Interações Hospedeiro-Patógeno/genética , Modelos Moleculares , Fases de Leitura Aberta , Fosfatos/química , Ligação Proteica , Conformação Proteica , Multimerização Proteica
15.
Arch Virol ; 165(6): 1289-1297, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32246283

RESUMO

Antimicrobial resistance is a serious threat to public health around the globe. According to the World Health Organization, there will be a return to the pre-penicillin era by 2050 if no new antimicrobials are discovered. It is therefore necessary to find new antimicrobials and alternatives. Pseudomonas aeruginosa exhibits resistance against many antibiotics and causes a variety of infections in immunocompromised individuals and especially in those with burn wounds and lung infections. Bacteriophage RLP against P. aeruginosa strain PA-1 was isolated from the Ravi River near Lahore. It showed marked stability at different pH values and temperatures, with the maximum storage stability at 4 °C. It demonstrated the ability to inhibit bacterial growth for up to 20 h, replicated in 25 min, and produced 154 virions per infected cell. RLP showed a broad host range, infecting 50% (19/38) of the multiple-drug-resistant (MDR) P. aeruginosa strains that were tested. The 43-kbp-long genome of RLP is a double-stranded DNA molecule that encodes 56 proteins in total: 34 with known functions, and 22 with no homolog in the gene databases. A cascade system of lytic machinery is also present in the form of four genes (R/z, R/z1, holin and endolysin). Therapeutic studies of RLP in bacteremic mice infected with P. aeruginosa strain PA-1 demonstrated a 92% survival rate in the treated group compared with 7.4% in the untreated group, and this result was statistically significant. Based on its physiological and genetic properties, ability to cause a reduction in bacterial growth in vitro and its in vivo therapeutic efficacy, RLP could be a good candidate for use in phage therapy.


Assuntos
Bacteriemia/terapia , Bacteriófagos/genética , Pseudomonas aeruginosa/virologia , Animais , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Bacteriófagos/ultraestrutura , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Feminino , Genoma Viral , Especificidade de Hospedeiro , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Pseudomonas aeruginosa/efeitos dos fármacos , Temperatura , Sequenciamento Completo do Genoma
16.
Epidemiol Mikrobiol Imunol ; 69(1): 10-18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32326711

RESUMO

AIM: Staphylococcus aureus strains are the cause of frightening hospital and community infections, especially when they are resistant to antimicrobials, have important pathogenicity factors, or have biofilm production ability. Looking for novel therapeutic options which would be effective against such strains is one of the highest priorities of medicine and medical research. The study aim was to describe the occurrence of S. aureus strains and proportion of methicillin resistant strains (MRSA) detected in laboratories of the Microbiological Institute, Faculty of Medicine, Masaryk University (FM MU) and St. Anne's University Hospital, Brno in 2011-2018. Selected strains of S. aureus were tested for biofilm production ability and susceptibility to antimicrobials and Stafal®, a phage therapeutic agent. A prerequisite was to develop a simple routine method suitable for phage susceptibility testing of bacteria. MATERIAL AND METHODS: Altogether 867 clinical isolates of S. aureus and 132 strains of other species of the genus Staphylococcus (isolated in 2011-2017) were tested for susceptibility to the phage therapy preparation Stafal® using the double-layer agar method. All strains of S. aureus were tested for biofilm production ability by the modified Christensen method with the use of titration microplates and for susceptibility to antistaphylococcal antibiotics by the disk diffusion test. For 95 S. aureus strains, the outcome of the double-layer agar method (DAM) was compared with that of our newly designed method (ODM) based on optical density decrease of the bacterial suspension. RESULTS: During the study period, the laboratories of the Faculty of Medicine, Masaryk University (FM MU) and St. Anne's University Hospital, Brno detected 2900 strains of S. aureus per year on average. The proportion of MRSA among S. aureus isolates from blood culture and venous catheters ranged between 8.8-15.2 %. S. aureus strains recovered from venous catheters and blood culture were confirmed as stronger biofilm producers than those from other clinical specimens. MRSA strains showed higher biofilm production than methicillin susceptible strains (MSSA). As many as 90.4 % of S. aureus strains tested susceptible to the Stafal® preparation. Even a higher proportion, i.e. 99.0 %, of MRSA strains were Stafal® susceptible. No relationship was found between Stafal® susceptibility and biofilm production ability. Although Stafal® targets primarily S. aureus, some susceptibility (26.5 %) was also found for other staphylococcal species. A novel simple method designed for routine testing of susceptibility to phage therapy preparations based on optical density decrease was comparably sensitive and reliable as the commonly used double-layer agar method (DAM) and, in addition to being easy and rapid to perform, after prolonged suspension culture and at higher measurement frequency, it has an extra advantage of providing the possibility for monitoring also phage action dynamics. CONCLUSIONS: The proportion of MRSA strains detected in this study is comparable to that reported for the whole Czech Republic, and the biofilm production data are consistent with scientific evidence. The host range of the Stafal® preparation is relatively wide and covers most strains of S. aureus and some coagulase negative staphylococci. The highest efficiency of Stafal® (99.4 %) was observed against MRSA strains with multiple types of antibiotic resistance. In vitro testing of 867 strains of S. aureus and 132 other staphylococcal species has shown the phage therapy preparation Stafal® to be a suitable candidate therapeutic option for the treatment of staphylococcal infections, especially in case of failure of conventional antibiotic therapy. Moreover, a simple method for routine phage susceptibility testing of clinical bacterial isolates has been designed, which is an essential tool to be used in phage therapy.


Assuntos
Bacteriófagos , Infecções Estafilocócicas , Staphylococcus , Antibacterianos/uso terapêutico , Bacteriófagos/fisiologia , República Tcheca , Humanos , Técnicas In Vitro , Staphylococcus aureus Resistente à Meticilina/virologia , Infecções Estafilocócicas/terapia , Infecções Estafilocócicas/virologia , Staphylococcus/virologia
17.
PLoS Comput Biol ; 16(3): e1007236, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32168336

RESUMO

Coexistence of bacteriophages, or phages, and their host bacteria plays an important role in maintaining the microbial communities. In natural environments with limited nutrients, motile bacteria can actively migrate towards locations of richer resources. Although phages are not motile themselves, they can infect motile bacterial hosts and spread in space via the hosts. Therefore, in a migrating microbial community coexistence of bacteria and phages implies their co-propagation in space. Here, we combine an experimental approach and mathematical modeling to explore how phages and their motile host bacteria coexist and co-propagate. When lytic phages encountered motile host bacteria in our experimental set up, a sector-shaped lysis zone formed. Our mathematical model indicates that local nutrient depletion and the resulting inhibition of proliferation and motility of bacteria and phages are the key to formation of the observed lysis pattern. The model further reveals the straight radial boundaries in the lysis pattern as a telltale sign for coexistence and co-propagation of bacteria and phages. Emergence of such a pattern, albeit insensitive to extrinsic factors, requires a balance between intrinsic biological properties of phages and bacteria, which likely results from coevolution of phages and bacteria.


Assuntos
Bacteriófagos/fisiologia , Microbiota/fisiologia , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Bacteriófagos/metabolismo , Quimiotaxia/fisiologia , Microbiota/genética , Modelos Teóricos , Reprodução Assexuada/fisiologia
19.
Lancet Infect Dis ; 20(5): e90-e101, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32213334

RESUMO

The use of bacteriophages to treat bacterial infections (known as phage therapy) is considered a possible solution to the antimicrobial resistance crisis. However, phage therapy is not a new concept. The discovery of phages in the early 20th century was closely tied to clinical practice, and phage therapy quickly spread around the world. The use of phage therapy in South America in the previous century is still shrouded in mystery and has been mentioned only briefly in recent scientific literature. Research on Brazilian reference collections of medical texts showed that Brazil was an important, but so far little-known, player of phage therapy, uncovering interesting priority claims and missing pieces of phage therapy history. Of note, there is the widespread use of phages against bacillary dysentery and staphylococcal infections, with José da Costa Cruz from the Oswaldo Cruz Institute (Rio de Janeiro, Brazil) as Brazil's leading expert and pioneer. This Historical Review about historical phage use in Brazil fills the gaps in our knowledge about the so-called golden years of phage therapy, providing information about successful experiences that can be useful against dangerous pathogens in our time.


Assuntos
Infecções Bacterianas/terapia , Infecções Bacterianas/virologia , Bacteriófagos/fisiologia , Brasil , Humanos , Terapia por Fagos/métodos
20.
Microb Genom ; 6(2)2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32111267

RESUMO

Paenibacillus larvae is a Gram-positive, spore-forming bacterium that is the causative agent of American foulbrood (AFB), the most devastating bacterial disease of the honeybee. P. larvae is antibiotic resistant, complicating treatment efforts. Bacteriophages that target P. larvae are rapidly emerging as a promising treatment. The first P. larvae phages were isolated in the 1950s, but as P. larvae was not antibiotic resistant at the time, interest in them remained scant. Interest in P. larvae phages has grown rapidly since the first P. larvae phage genome was sequenced in 2013. Since then, the number of sequenced P. larvae phage genomes has reached 48 and is set to grow further. All sequenced P. larvae phages encode a conserved N-acetylmuramoyl-l-alanine amidase that is responsible for cleaving the peptidoglycan cell wall of P. larvae. All P. larvae phages also encode either an integrase, excisionase or Cro/CI, indicating that they are temperate. In the last few years, several studies have been published on using P. larvae phages and the P. larvae phage amidase as treatments for AFB. Studies were conducted on infected larvae in vitro and also on hives in the field. The phages have a prophylactic effect, preventing infection, and also a curative effect, helping resolve infection. P. larvae phages have a narrow range, lysing only P. larvae, and are unable to lyse even related Paenibacillus species. P. larvae phages thus appear to be safe to use and effective as treatment for AFB, and interest in them in the coming years will continue to grow.


Assuntos
Bacteriófagos/fisiologia , Abelhas/microbiologia , Paenibacillus larvae/virologia , Animais , Bacteriófagos/genética , Genoma Viral , Paenibacillus larvae/fisiologia
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