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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
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