Emerging Antibiotic Resistance in Mycoplasma Microorganisms, Designing Effective and Novel Drugs / Therapeutic Targets: Current Knowledge and Futuristic Prospects

Abstract

Emerging antibiotic resistance among mycoplasma microorganisms is of major concern in present times as they cause various diseases in both animals and humans. Mycoplasmoses, infections caused by mycoplasma microorganisms have become common in recent past and have gained importance both due to inability to diagnose and difficulty to treat. Respiratory tract infection, mastitis, arthritis, and septicemia caused by Mycoplasma in livestock are responsible for causing heavy economic losses. These diseases are frequently reported from countries of Africa and Asia, including India. Antimycoplasma antibiotics are frequently being used as therapeutic agents for the treatment of mycoplasmoses infection in livestock. They include macrolides, tetracyclines, fluoroquinolones, and aminoglycosides which are the main antibiotic classes commonly used against mycoplasma globally. Oxytetracyclines are the commonest antibiotics used for decades followed by enrofloxacin, tylosin, and streptomycin. Danofloxacin, lincomycin, spiramycin, erythromycin, gamithromycin, azithromycin, clarithromycin, gentamicin, doxycycline, and tulathromycin are also used occasionally. Continuous and unregulated use of these antibiotics over prolonged period can lead to menace of antibiotic resistance which is aided by inappropriate doses and uncontrolled use. Resistance to some antibiotics is already emerging. Mycoplasmas have devised different resistance mechanisms for combating antimicrobial action of these drugs. Common mechanisms noted are acquisitions of proteins affecting ribosomal subunits, inhibition of antibiotic efflux, structural changes in the ribosomal subunit, target mutations, expression or production of enzymes. Additional novel mechanisms of resistance still need to be investigated. Strategies for prevention and encountering of this antibiotic resistance are being devised by alternating antibiotics in application, using antimycoplasma antibiotic sensitivity tests, along with evaluation of specific doses and exploration of novel mycoplasma specific class of antibiotics. Novel targets based on various cell structures including cell membrane, organelles, proteins, enzymes or metabolites are being explored for antimycoplasma therapy. These all will help in effective therapeutic management of mycoplasmoses with minimal side effects.

Novel Candidates for Vaccine Development Against Mycoplasma Capricolum Subspecies Capripneumoniae (Mccp)—Current Knowledge and Future Prospects

“…Treatment by antibiotics as the only therapeutic strategy for CCPP is not a viable option due to the persistence of Mccp pathogens in treated animals, which act as disease carriers [5,41]. Besides, large-scale and repeated antibiotic treatments of herds cause economic constraints for farmers due to the expense and concerns for antibiotic resistance [4,5,14,27,40,42,43]. Hence, the role of prophylactics, such as vaccines, is becoming imperative under the current scenario in order to prevent CCPP outbreaks and control its spread [2,41,44].…”

“…Such exploration needs to be extended to include other components. In addition to the capsule, the plasma membrane, ribosomes, nuclear material, enzymes, and metabolites may have potential roles in virulence and antigenicity [20,42]. Utilization of hyperimmune serum against CCPP needs to be evaluated for prophylaxis as it can boost immunity and may be therapeutic during outbreaks, since it can provide an instant antibody that neutralizes pathogenic mechanisms [15,17,19,62,83].…”

“…However MmmLC and Mmc have been grouped in single subspecies. These six members of the mycoides cluster are antigenically related, as they share some common antigens [21,42,67,85,86,87]. Hence, cross-reactions are frequently noted in diagnostic tests [54,55].…”

“…In our previous review, we summarized possible future therapeutic targets for Mycoplasma infections [42]. These targets include structural units, proteins, enzymes, metabolites, or genes and other genetic material.…”

“…DNA-related targets include mutant genes [113], targeted chromosomal knockouts [114], the QRDR region (DNA gyrase and topoisomerase IV) [101], 30S ribosomal subunit [101,115], 50S ribosomal subunit [101,115], domains II and V of the 23S rRNA gene, and the ribosomal protein L4 and L22 genes [112]. Metabolites that are possible virulence factors include hydrogen peroxide [106], glycerol [106,116], or oxidative radicals [42].…”