Abstract
Streptococcus pneumoniae is highly pathogenic and causes several mucosal and invasive infections. Due to the rising number of multidrug-resistant (MDR) strains of S. pneumoniae, new antimicrobials with alternative mechanisms of action are urgently needed. In this study, we identified two new Streptococcal phages from the oral microbiome, 23TH and SA01. Their lysins, 23TH_48 and SA01_53, were recombinantly expressed, characterized and tested for their lethality. SA01_53 was found to only lyse its host strain of S. anginosus, while 23TH_48 was found to possess a broader lytic activity beyond its host strain of S. infantis, with several S. pneumoniae isolates sensitive to its lytic activity. 23TH_48 at a concentration of five activity units per mL (U/mL) was found to reduce cell counts of S. pneumoniae DSM 24048 by 4 log10 colony forming units per mL (CFU/mL) within 1 h and effectively prevented and destroyed biofilms of S. pneumoniae R6 at concentrations of 228.8 ng/µL and 14.3 ng/µL, respectively. Given its high lytic activity, 23TH_48 could prove to be a promising candidate to help combat pneumococcal infections.
Highlights
Streptococcus spp. are found in the upper respiratory tract, the intestine, on the skin, and are the dominant species in the human oral cavity
We describe two new phage lysins (23TH_48 and SA01_53) encoded by phages isolated from the oral microbiome (23TH and SA01)
Phages 23TH and SA01 were isolated from human saliva against the target strains Streptococcus infantis 23TH and Streptococcus anginosus SA01, respectively
Summary
Streptococcus spp. are found in the upper respiratory tract, the intestine, on the skin, and are the dominant species in the human oral cavity. Infections range from mild throat infections to systemic and life-threatening diseases such as streptococcal pharyngitis, Scarlett fever, necrotizing fasciitis, and toxic shock syndrome. One of these highly pathogenic species is Streptococcus pneumoniae, which can cause pneumonia, otitis, meningitis, and sepsis [2]. Invasive pneumococcal diseases can be prevented with vaccines targeting the capsular polysaccharides (CPs) of pneumococcal strains. These multivalent vaccines are limited to between 10 to 13 of the 97 known CP types [5], leading to incomplete protection. The development of pneumococcal resistance to commonly used antibiotics, such as penicillins, macrolides, tetracyclines, and fluoroquinolones is causing worldwide concern [8]
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