The ΦCPG1 chlamydiaphage can infect Chlamydia trachomatis and significantly reduce its infectivity

Recent years have seen a significant increase in rates of persistent, antibiotic-resistant infection of Chlamydia trachomatis (CT) infections, representing an increasingly serious public health threat. At present there are no effective vaccines or antibodies available to treat CT, prompting the need for novel treatment strategies. One potential solution to this issue is the use of ΦCPG1, a chlamydia-specific lytic phage which has over 90% nucleotide sequence identity with other chlamydiaphages. Previous work has shown the Vp1 capsid protein of ΦCPG1 to exhibit broad inhibitory activity against all CT serotypes, inhibiting CT-mediated host cell toxicity. Patients with CT infections exhibit circulating antibodies against this Vp1 protein, suggesting that this or similar phages may be present in vivo in the context of CT infections, even though no phages have been specifically detected to date. Given these previous findings, we hypothesized that the ΦCPG1 chlamydiaphage may be able to infect CT, thereby inhibiting its growth and proliferation. To test this, we generated a recombinant pGFP-ΦCPG1 phage which we used to explore its effects on CT and chlamydia conjunctivitis of guinea pigs (GPIC). We found that pGFP insertion did not alter the packaging or infectivity of ΦCPG1, and that this recombinant phage was readily able to infect CT and GPIC and inhibit CT and GPIC in a dose-dependent fashion. This inhibition was most pronounced during the mid and late stages of the CT infection, disrupting the reticular body (RB) to EB transition, leading to the formation of enlarged RBs. These results indicate that ΦCPG1 is able to infect CT, highlighting this phage as a novel potential therapeutic agent for treating chlamydia infections. In addition, by engineering pGFP to express ΦCPG1, we have produced an valuable experimental tool useful for future studies of drug resistance, pathogenicity, and vaccine research aimed at improving CT treatment.