Nanomaterials to Overcome Emergence and Re-Emergence of Superbugs: Nanoarsenals for Superbugs

1.1 Concept of Emergence and Re-Emergence of Superbugs

Approximately 70 years ago, antibiotics were introduced to cure infectious diseases. These are the drug molecules used to kill bacteria and they reduce the risk associated with various infections. Antibiotics exhibited their action by inhibiting the proliferation process of bacteria. Overtime, antibiotics started showing resistance to different bacteria’s called superbugs (Drug-resistant microbes). Antibiotic resistance is the tolerance developed by bacteria to overcome the effects of antibiotics (https://www.statnews.com/2016/09/12/superbug-antibiotic-resistance-history/, Ventola, 2015). Also, Klebsiella pneumonia causes fatal and untreatable infections in a healthy population. It may cause a danger to life of individual (Gu et al., 2018). Some other examples of antibacterial discovery with their resistance are given in Figure 1.

Figure 1.

History of antibiotic discovery

World Health Organization (WHO) has already warned about the emergence of infectious diseases at a faster rate which has never seen before (https://www.sciencedaily.com/releases/2017/08/170831101508.html). Some of the re-emerging diseases with a causative agent are given in Table 1. The re-occurrence of old infections along with emergence of new infectious diseases and constant persistence of various intractable infections is a major challenge to the researchers.

One of the reasons for antibiotic resistance is a development of biofilms. Most of the bacterial strains occur in the form of a biofilm which are especially microbial aggregates that rely on a solid surface and extracellular products such as extracellular polymeric substances (EPS’s). Bacteria tend to move reversibly on the surface, but the expression of EPSs makes this attachment irreversible. After settlement of bacteria, the synthesis of bacterial flagellum is suppressed and rapid multiplication of bacteria results in the formation of a mature biofilm. They all are in aggregates at this stage and forms a barrier for antibiotic action which led to systemic chronic infections. Bacteria within biofilms develop superantigens that tend to evade the immune system. Thus, the formation of biofilms is a serious threat to human health and makes infection control more challenging (Frieri et al., 2017, Von Wintersdorff et al., 2016). These biofilms are embedded into extracellular polymeric substances (EPS) matrix. The EPS is composed of phospholipids, nucleic acids, teichoic acid, exopolysaccharides and extracellular proteins. In addition, mineral crystals, silt, milk residues and blood parts or dirt may be present in EPS matrix, depending upon the location and conditions under which biofilm is formed (Ramos et al., 2018). The biofilm tends to adhere irreversibly to organic phenomenon or biotic surfaces and 80% of pathogenic infections remain persistent due to this biofilm. For example, P. aeruginosa (linked to cystic fibrosis) and Staphylococcus aeruginosa (accountable for wound infections) are traditional examples of persistent pathogens that lead to formation of biofilm (Algburi et al., 2016). The formation of micron size biofilms occurs around solid surfaces in contact with water, like living tissues and water bodies/systems (Clatworthy et al., 2007). The development of a biofilm involves various steps i.e. adhesion, growth, and production of EPS matrix. A cycle indicating the 5 stages is discussed below (Ramos et al., 2018) (Figure 2) and strategies for prevention of biofilm is shown in Figure 3.

Stage 1: This involves deposition of bacterial cells when the microbes arrive to site of adhesion and macromolecules present on that site act as the substrate for these microbial cells which lead to formation of biofilm (Myszka et al., 2011).

Stage 2: A reversible adhesion of bacterial cells is followed by communication between the cells which are associated with cells of next stage. The EPS matrix is formed during this stage (Wilkins et al., 2014).

Stage 3: This stage involves enhanced EPS production that ends up in a rise of bacterial cells. The matrix formed act as a reservoir for genetic material to alter gene transfer, to supply nutrients and to protect against adverse conditions like exposure to biocides, antibiotics, drying, oxidation, certain metallic cations, ultraviolet (UV) radiations, etc. The assembly of the matrix represents the formation of biofilm communities, propagation and survival of bacterial cells in their native environment (O’toole et al., 2000).

Stage 4: At this stage, biofilm gets matured by forming characteristic “mushroom” structures due to polysaccharides.

Stage 5: Finally some cells start to detach and the biofilm will disperse (https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/biofilms-and-their-role-in).

Figure 2.

Various stages of biofilm formation

Figure 3.

Strategies for the prevention of biofilm