Biofilm: A Robust and Efficient Barrier to Antifungal Chemotherapy

Souza dos Santos AL, de Mello TP
2015 Journal of Antimicrobial Agents  
Editorial Fungal diseases affect a considerable proportion of the worldwide population, ranging in severity from mild superficial infections to grave invasive diseases [1] [2] [3] [4] [5] [6] [7] . The emergence and spread of systemic life-threatening fungal infections have increased in the last three decades, causing a major and alarming global concern [1-7]. The more widespread provision of new medical practices (e.g., immunosuppressive therapy, use of broad spectrum antibiotics and invasive
more » ... otics and invasive surgical procedures such as solid organ and bone marrow transplantation) and the greater number of people suffering from predisposing conditions (e.g., immunocompromising status such as neutropenia, diabetes and human immunodeficiency virus infection, low-birth-weight newborns, burns, patients with cancer and critically ill patients requiring implanted medical devices or grafts) are the main factors that have been implicated in the augmented number of fungal infections [8] [9] [10] [11] [12] (Figure 1 ). The high morbidity and mortality associated with fungal infections is compounded by the limited therapeutic options and the emergence of drug-resistant fungi [13] [14] [15] [16] [17] . Timely and adequate interventions are necessary to maximize favorable outcomes, culminating in a successful treatment. Improved antifungal strategies are therefore urgently required [13] [14] [15] [16] [17] . In this context, the anti-virulence strategy is in vogue and is a light at the end of the tunnel considering the limited antifungal armamentarium [18] [19] [20] . In theory, the anti-virulence therapy prevents the emergence of resistance against a particular drug, since it inhibits the expression of virulence attribute(s) that are essential for the development of infection, without inhibiting the microbial proliferation [18] [19] [20] . Fungi are able to produce an arsenal of virulence factors [21] [22] [23] [24] , including the ability to form biofilm in both biotic (e.g., host tissues such as the oral cavity, respiratory, gastrointestinal and urinary tracts) and abiotic surfaces (e.g., implanted medical devices such as venous catheters, cannulation, pacemakers, endotracheal tubes, ventriculoperitoneal shunts, prosthetic joints, breast implants, contact or intraocular lenses, stents, intrauterine contraceptive devices and dentures) [24] [25] [26] [27] . Alarming statistics on this theme corroborate the relevance of biofilm-related diseases: (i) the National Institutes of Health (NIH, USA) estimated that microbial biofilms (including both bacterial and fungal biofilms) were responsible for over 80% of all infections in USA [28], (ii) approximately 500,000 intravascular device-related bloodstream infections occur in USA each year [29], (iii) the majority of bloodstream infections are caused by infected central venous catheters, which is correlated with prolongation of hospital stay and added costs to the health care system, resulting in an estimated cost of US$ 11 billion annually [30] [31][32]. Biofilm is the predominant growth lifestyle of many microorganisms, including several human opportunistic fungal pathogens (e.g., Candida albicans, non-albicans Candida species, Cryptococcus neoformans, Cryptococcus gatti, Trichosporon asahii, Rhodotorula spp., Aspergillus fumigatus, Malassezia pachydermatis, Histoplasma capsulatum, Coccidioides immitis, Pneumocystis spp., Fusarium spp. and many others), and is defined as a community of microorganisms encapsulated in a self-produced extracellular polymeric substance (or extracellular matrix) attached to a surface [33][34][35][36]. The biofilm extracellular matrix is mainly composed by polysaccharides, proteins, lipids and DNA, which form a robust shelter that offers a protected and nutritionally rich environment, contributing to survival, molecule exchanges and proliferation [37]. The analysis of the A. fumigatus biofilm extracellular matrix by solid-state nuclear magnetic resonance spectroscopy revealed approximately 43% polysaccharide, 40% protein, 14% lipid and 3% aromatic-containing components [38]. The formation of a microbial biofilm can be didactically summarized in five sequential steps: (i) adherence of cells to a surface, (ii) initial formation of colonies, (iii) secretion of extracellular polymeric substances, (iv) maturation in a three-dimensional structure and (v) cell dispersion [39]. Taking into account the clinical perspective, biofilms are intrinsically resistant to (i) conventional antifungal drugs, (ii) host immune responses and (iii) several environmental stress conditions,
doi:10.4172/2472-1212.1000e101 fatcat:xp6mrwievncevn57t7txoaoxju