Current alternative therapies for treating drug-resistant Neisseria gonorrhoeae causing ophthalmia neonatorum

Abstract

Ophthalmia neonatorum is a microbial contraction, damaging eyesight, occurring largely among neonates. Infants are particularly vulnerable to bacterial infections acquired during birth from infected mothers, especially from Neisseria gonorrhoeae and Chlamydia trachomatis. Over the decades, N. gonorrhoeae is alarmingly developing a resistance to most antibiotics currently prescribed. To counter this challenge, it is imperative to find potent and cost-effective therapeutic agents for prophylaxis and treatment, to which the N. gonorrhoeae cannot easily develop resistance. This review showcases alternate therapies such as antimicrobial-fatty acids, -peptides, -nano-formulations etc., currently evident against N. gonorrhoeae-mediated ophthalmia neonatorum, which remains a major cause of ocular morbidity, blindness and even death among neonates in developing countries.

Plain language summary

Gonorrhea is a sexually transmitted infection caused by the bacteria Neisseria gonorrhoeae. N. gonorrhoeae can infect a newborn's eyes during birth by an infected mother. These babies can develop redness, irritation and discomfort in the eye(s), a condition called ophthalmia neonatorum. This condition can lead to blindness. Antibiotics are used to treat N. gonorrhoeae infections, but in recent decades, it has been fast evolving to avoid the action of most antibiotics. This is known as antibiotic resistance. There is, therefore, an urgent need for easily accessible non-antibiotic therapies. In this article, various alternate therapies currently available to treat N. gonorrhoeae have been reviewed.

Executive summary

Bald's eyesalve against N. gonorrhoeae

• A natural extract recipe such as Bald's eyesalve can have anti-gonococcal effect [52,53] and also significant anti-bactericidal effect on both biofilm and planktonic bacteria.

• Safety profile testing of Bald's eyesalve indicate least toxicity and irritability on the viability of human cells [52,53].

Fatty acids & monoglycerides as antimicrobials against N. gonorrhoeae

• Along with rapid antimicrobial activity, absence of irritation, and inability to develop resistance, fatty acids (FA) and their derivatives serve as auspicious agents both for prophylaxis and treatment of bacterial infection caused by N. gonorrhoeae and a range of microbial species, signifying the potential options for biomedical applications.

• The inducible resistant phenotypes developed against free fatty acids is least problematic than those developed with conventional antibiotics.

• α-linolenic acid-based microemulsions are effective against bacterial eye infections for the treatment of ophthalmia neonatorum caused by N. gonorrhoeae.

• In the absence of vaccines, the administration of monocaprin could be novel prophylaxis that could check gonococcal growth and colonization.

• Neisseria gonorrhoeae could not develop resistance against monocaprin [59] in contrast to other antibiotics employed in treating ophthalmia neonatorum.

Anti-Neisseria peptides against N. gonorrhoeae

• All anti-Neisseria peptides currently available are cationic and harbor hydrophobic domains necessary for bactericidal activities.

• They harbor both alpha-helix (LL-37, LSA-5, Bmkn2) or beta sheet structure (TP-1, HE2, PG-1) are correlated with action of membrane degradation and osmotic lysis.

• Strong binding of cationic peptides to LPS disrupts the integrity of the outer membrane as well as enhances the permeability of the outer membrane to hydrophobic antibiotics.

• AMPs can be used as adjuvants in combination with current antibiotics in order to combat antibiotic resistance so that it is unlikely to develop resistance or transmit cross-resistance. Notably, action of antibiotics can be further boosted with synergistic effect of AMPs such as HE2.

• AMPs such as Protegrins, HE2, Mutacin B-Ny266 have bactericidal effect on drug-resistant N. gonorrhoeae strains.

Fabricated nano-formulations against N. gonorrhoeae

• Ag NPs with ceftriaxone [90], MNBA-AgNCs [87], chitosan NPs [89], silver delafossite oxide (AgCuO₂) [91] displayed remarkable anti-gonococcal activity with minimal cytotoxicity.

• MNBA-AgNCs is shown greater gonococcal activity in vitro than ceftriaxone and azithromycin [87] and also effectively kills planktonic and multiple aggregates of bacteria during infection of human cells in vitro.

• AS101 significantly prevents in vitro both the formation and growth of gonococcal microcolonies, and reduced the pre-formed biofilm growth and induces higher ROS levels in a dose-dependent manner [88].

• Nano-formulated mupirocin kills effectively ceftriaxone-resistant Neisseria gonorrhoeae [92].

Keywords: :

• antimicrobial peptides (AMPs)
• antimicrobial resistance (AMR)
• Bald's eyesalve
• fatty acids (FA)
• monocaprin
• Neisseria gonorrhoeae
• ophthalmia neonatorum (ON)

Financial disclosure

The author has no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The author has no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.