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= Endolysins as a biological alternative for the treatment of multidrug-resistant bacteria. =

Indiscriminate use of antibiotics
The systematic use and abuse of antimicrobials triggered the spread of antibiotic-resistant bacteria, a situation that is now considered a priority by the World Health Organization (WHO), the World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO). This is further reinforced by the approach taken by the WHO, which determines that antibiotics administered to food-producing animals should only be used to treat infectious diseases and not for growth promotion, as is the case today on many farms around the world, as well as in Bolivia.

In recent decades, the isolation and identification of antibiotic-resistant bacteria, resistant to at least 3 of the 13 categories of antibiotics, has been reported as a direct effect of the indiscriminate use of antibiotics in human and veterinary medicine, as well as in industry and agriculture.

A substantial factor to consider is that multi-drug resistance (MDR) bacteria can be transmitted by zoonosis or through the food chain and the environment. Therefore, under the "One-Health" concept, it is imperative that efforts to control the spread of antibiotic resistant bacteria and/or antimicrobial resistance genes be directed towards the proposal of alternative control methods that do not involve environmental contamination and do not affect human and animal health.

The problem of multi-drug resistant bacteria in Bolivia
A major health problem in Bolivia is food- and water-borne infections, mainly due to poor agricultural practices, improper or absent basic sanitation procedures, poor food handling practices, and poor or absent wastewater treatment. Among the most common infectious diseases are those caused by Salmonella, Escherichia coli and Campylobacter strains.

Bacteriophages as an alternative
One of the promising "new" approaches that is increasingly being highlighted, among others, is therapy with phages or bacteriophages (viruses that infect bacteria). Bacteriophages have a number of advantages over other alternatives: (i) high efficacy in killing bacteria, (ii) minimal or no side effects, (iii) no allergic effects, (iv) production is rapid and inexpensive, and (v) they are host-specific and therefore do not affect the intestinal microbiota or other saprophytic bacteria in the environmental milieu.

Different scientific studies have shown that the use of bacteriophages is effective in the prevention and treatment of bacterial pathogens in animals. In the specific case of poultry, good results have been obtained by reducing the infection of Salmonella, E. coli and Campylobacter. Until now, the use of phage therapy to control Salmonella in poultry could reduce, but not completely eliminate bacterial colonisation.

Much research remains to be done to ensure that bacteriophages can become effective in the treatment of different bacterial infections, including the need for bacteriophages to be present in high concentrations and stable enough to reach the site of infection in an active state.

Poultry farm and food sanitation
Salmonellosis is particularly costly for livestock farmers, so control is mainly based on cleaning niches with strong acids or specialized detergents of livestock type, also large amounts of water are used, because to remove organic matter and biofilms formed by bacteria, pressurized water is used, in order to remove all residues of contamination.

Farmers often use feed that has been supplemented with antibiotics to prevent salmonellosis and other bacterial infections in their animals, justifying that if an animal loses too much weight due to the disease, there will not be enough meat to sell for profit, and the cost of treating infections is considered high.

Salmonellosis in the poultry sector
Poultry are a source of pathogens such as Salmonella, Clostridium perfringes and Campylobacter. The presence of poultry salmonellosis in farms causes losses to producers in addition to turning them into sources of contamination and dissemination of strains. Studies conducted by Cordero & Guardia, 2021 on the incidence of Salmonella spp (immobile), in laying hens in the department of Cochabamba - Bolivia during the period from September 2018 to September 2019, confirmed positive cases, equivalent to 29%, being prevalent especially in fecal samples, where despite vaccines it is not completely eliminated.

The Salmonella serotypes with the highest prevalence in poultry farms are:  Salmonella Enteritidis and Salmonella Typhimurium, however, during the last years the presence of Salmonella Heidelberg and Salmonella Infantis was also reported.

The ability of Salmonella to form biofilms and remain for long periods of time in poultry niches is a latent danger, because since it was discovered that antibiotics in subtherapeutic doses administered in food promoted the growth of poultry, pigs and cattle, most antibiotic production has been destined for animal consumption, where approximately 90% is excreted in the feces, allowing the bacteria present to generate resistance mechanisms to these antibiotics. For this reason, the international arena highlights the potential role of poultry and layer farm environments as reservoirs of MDR strains of Salmonella, in addition to their capacity to be transmitted through plasmids to other bacteria.

Biological control
Biological control is the use of any living organism and/or its by-products to combat any specific disease, pathogen or pest through parasitism, antibiosis, competition for resources or space or by developing immunity against them.

Populations of all organisms are reduced to some extent, by natural actions of their predators, parasites, antagonists and diseases, this process is known as "natural control", but when pests are controlled it is called biological control or biocontrol and the agents exerting control are called natural enemies, and it differs significantly depending on whether the pests are invertebrates, plants or microorganisms.

Bacteriophages as biocontrol tools for pathogenic and/or antibiotic resistant bacteria.
Bacteriophages are suitable to prevent or reduce the colonization of pathogenic bacteria and therefore diseases in cattle, where phages are supplied either individually or in cocktail to farm animals, the routes and methods of application were examined by various authors and the application of phages through oral tube feeding or feed intake showed a reduction of pathogenic bacteria without affecting the intestinal microbiota of the host. Current research is focused on improved phage delivery in a manner that avoids decreasing phage titer due to destabilization or inactivation by gastric pH extremes.