MAJOR ARTICLE Bacteriophage Therapy and MDR P. aeruginosa • JID 2019:219 (1 May) • 1439 The Journal of Infectious Diseases Received 1 October 2018; editorial decision 16 November 2018; accepted 20 November 2018; published online November 22, 2018. Correspondence: Y. M. Ali, Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt (m_youssif@mans.edu.eg). The Journal of Infectious Diseases ® 2019;219:1439–447 © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/infdis/jiy678 Bacteriophage Terapy Increases Complement-Mediated Lysis of Bacteria and Enhances Bacterial Clearance Afer Acute Lung Infection With Multidrug-Resistant Pseudomonas aeruginosa Abeer M. Abd El-Aziz, Abdelaziz Elgaml, and Youssif M. Ali Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Egypt Emergence of multidrug-resistant (MDR) bacterial infections is a major problem in clinical medicine. Development of new strate- gies such as phage therapy may be a novel approach for treatment of life-threatening infections caused by MDR bacteria. A newly isolated phage, MMI-Ps 1 , with strong lytic activity was used for treatment of acute lung infection with Pseudomonas aeruginosa in a mouse model. Intranasal administration of a single dose of MMI-Ps 1 immediately afer infection provided a signifcant level of protection and increased the survival duration. Moreover, treatment of infected mice with phage as late as 12 hours afer infection was still protective. Our in vitro results are the frst to show the synergistic elimination of serum-resistant Pseudomonas strains by phage and complement. Phage therapy increases the efcacy of complement-mediated lysis of serum-resistant P. aeruginosa strains, indicating the importance of an intact complement system in clearing Pseudomonas infection during phage therapy. Keywords. Multidrug-resistant bacteria; Pseudomonas aeruginosa; lung infection; bacteriophage; phage therapy; complement system. Pseudomonas aeruginosa is a worldwide pathogen responsible for a wide range of bacterial complications, including urinary tract infection, burn infection, and pneumonia [1]. P. aerugi- nosa was reported to be the most common microorganism iso- lated from hospitalized patients, and it accounts for 10% of all hospital-acquired infections, placing it among the 3 most fre- quently reported nosocomial pathogens [2]. Antibiotic resistance has become one of the world’s most important public health concerns. Te promiscuous misuse of antibiotics, especially in developing countries where antibi- otics can be taken without medical prescription, has led to an extensive spread of multidrug-resistant (MDR) bacteria [3, 4]. A recent report by the World Health Organization showed that approximately 50% of P. aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Escherichia coli infections were re- sistant to newly discovered and potent antibiotics [5]. In addi- tion, MDR bacteria were associated with high rates of mortality in Europe and the United States, accounting for around 25 000 and 23 000 deaths per year [4]. Antibiotics are considered the frst line of medication for treatment of bacterial infections; however, evolution of MDR bacteria has led to fear of a postanti- biotic era, in which many bacterial infections will be untreatable with conventional antibiotics [6–8]. Tus, it is necessary to ex- plore new strategies for treatment of bacterial infections [8, 9]. Currently, many studies have been established to develop al- ternative therapies with novel mechanisms of action to achieve antibacterial activity and ensure that a robust pipeline of ef- fective therapies is available to clinicians. Tese approaches include bacteriophage therapy, quorum-sensing quenching, iron chelation therapy, antimicrobial peptide therapy, and vac- cination [4, 9, 10]. Among these approaches, bacteriophage therapy has received the most attention [11]. Bacteriophages are viruses that have the ability to infect and lyse bacteria. Te host specifcity of bacteriophages is very strong, and they can be specifc for particular strains even among a single bacte- rial species. However, there are some bacteriophages that have the ability to infect multiple species [12, 13]. Historically, use of bacteriophages as therapeutic agents was very common in the eastern hemisphere before antibiotic discovery; however, it was never totally afrmed in the western hemisphere [4, 11, 14]. Treatment of bacterial infection with bacteriophage has several advantages over traditional antibiotic therapy. Tey are highly specifc for bacteria and even particular strains and species of bacteria, they do not afect human cells, and, if appropriately chosen, they have little or no efect on normal microbial fora. Downloaded from https://academic.oup.com/jid/article/219/9/1439/5199417 by guest on 25 January 2022