Nanomaterials for alternative antibacterial therapy

Abstract

Despite an array of cogent antibiotics, bacterial infections, notably those produced by nosocomial pathogens, still remain a leading factor of morbidity and mortality around the globe. They target the severely ill, hospitalized and immunocompromised patients with incapacitated immune system, who are prone to infections. The choice of antimicrobial therapy is largely empirical and not devoid of toxicity, hypersensitivity, teratogenicity and/or mutagenicity. The emergence of multidrug-resistant bacteria further intensifies the clinical predicament as it directly impacts public health due to diminished potency of current antibiotics. In addition, there is an escalating concern with respect to biofilm-associated infections that are refractory to the presently available antimicrobial armory, leaving almost no therapeutic option. Hence, there is a dire need to develop alternate antibacterial agents. The past decade has witnessed a substantial upsurge in the global use of nanomedicines as innovative tools for combating the high rates of antimicrobial resistance. Antibacterial activity of metal and metal oxide nanoparticles (NPs) has been extensively reported. The microbes are eliminated either by microbicidal effects of the NPs, such as release of free metal ions culminating in cell membrane damage, DNA interactions or free radical generation, or by microbiostatic effects coupled with killing potentiated by the host's immune system. This review encompasses the magnitude of multidrug resistance in nosocomial infections, bacterial evasion of the host immune system, mechanisms used by bacteria to develop drug resistance and the use of nanomaterials based on metals to overcome these challenges. The diverse annihilative effects of conventional and biogenic metal NPs for antibacterial activity are also discussed. The use of polymer-based nanomaterials and nanocomposites, alone or functionalized with ligands, antibodies or antibiotics, as alternative antimicrobial agents for treating severe bacterial infections is also discussed. Combinatorial therapy with metallic NPs, as adjunct to the existing antibiotics, may aid to restrain the mounting menace of bacterial resistance and nosocomial threat.

Keywords: antibacterial; antibiotic resistance; metallic nanoparticles; microbial biofilms; microbicidal; nanomedicines.

Figure 1

Strategies for survival in the host to spark invasive infections. (A) Innate immune mechanisms evaded by bacteria include phagocyte (macrophages, neutrophils) recruitment and activation, opsonization via Fc receptors on macrophages, complement activation and the bactericidal activities of antimicrobial peptides and reactive oxygen species. (B) Drug resistance mechanisms evolved by bacteria comprise hydrolysis by β-lactamases, modification of drug targets or antibiotics, loss or mutation of porins and overexpression of efflux pumps. Abbreviations: AMP, antimicrobial peptide; ROS, reactive oxygen species; AME, aminoglycoside-modifying enzyme; MDR, multidrug resistant; LPS, lipopolysaccharide.

Figure 2

Probable nanomaterials-based bactericidal effects. Nanomaterials trigger release of heavy metal ions that intercalate between bases, damage cellular proteins, disrupt cell signaling, generate free radicals and prevent biofilm formation. Abbreviation: ROS, reactive oxygen species.