Surface-associated bacterial communities called biofilms are ubiquitous in nature. Biofilms are detrimental in medical settings due to their high tolerance to antibiotics and may alter the final pathophysiological outcome of many healthcare-related infections. Several innovative prophylactic and therapeutic strategies targeting specific mechanisms and/or pathways have been discovered and exploited in the clinic. One such emerging and original approach to dealing with biofilms is the use of human milk oligosaccharides (HMOs), which are the third most abundant solid component in human milk after lactose and lipids. HMOs are safe to consume (GRAS status) and act as prebiotics by inducing the growth and colonization of gut microbiota, in addition to strengthening the intestinal epithelial barrier, thereby protecting from pathogens. Moreover, HMOs can disrupt biofilm formation and inhibit the growth of specific microbes. In the present review, we summarize the potential of HMOs as antibacterial and antibiofilm agents and, hence, propose further investigations on using HMOs for new-age therapeutic interventions.

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Klebsiella pneumoniae is one of the leading causes of community and nosocomial infections. Reduced treatment options against extensively drug resistant (XDR) - K. pneumoniae, is a serious concern in hospital settings, and hence, WHO has categorized it as a critical priority pathogen. Biofilm forming ability is a common virulence mechanism amongst K. pneumoniae that is associated with antibiotic tolerance up to 1000X MIC and hence, are difficult to treat. N-acetyl cysteine (NAC) is an FDA approved mucolytic drug used to treat acetaminophen-associated toxicity and obstructive pulmonary diseases. In this study, we assessed antibacterial and antibiofilm activity of NAC against clinical isolates of XDR K. pneumoniae, obtained from Madras Medical Mission Hospital, India. To assess the biofilm eradication ability of NAC, we grew biofilms in 96 well plates and treated the mature biofilms with different concentrations of NAC. We observed that the biofilms of only 3 isolates of XDR K. pneumoniae could be eradicated at a concentration as low as 20mg/ml. Although increasing the concentration of NAC to 80mg/mL could significantly reduce the biofilms of all the isolates up to 4-5 Log, NAC at a concentration of 100 mg/mL successfully eradicated the mature biofilms of all the isolates of XDR K. pneumoniae. This in vitro study demonstrates the potential of NAC as an efficient agent against the biofilms of clinical isolates of XDR-K. pneumoniae and thus provides a promising alternative to antibiotics.