Effect of Chlamydiaphage φCPG1 on the Course of Conjunctival Infection with “ Chlamydia caviae ” in Guinea Pigs

Abstract

Over the last several years, four different phages of chlamydiae, in addition to a phage associated with Chlamydia psittaci isolated from an ornithosis infection in ducks over 25 years ago, have been described and characterized. While these phages and their chlamydial host specificities have been characterized in vitro, there is virtually nothing known about the interaction of the phage with chlamydiae in their natural animal host. CPG1 is a lytic phage specific for "Chlamydia caviae," which is a natural parasite of the guinea pig. In this study, guinea pigs were inoculated in the conjunctiva with suspensions of CPG1 and C. caviae and the effect on the development of pathology and on the course of chlamydial infection in the conjunctiva was determined. The presence of phage delayed the appearance of the peak level of chlamydiae in the animal and decreased the pathological response. Evidence for replication of the phage in C. caviae in the conjunctival tissue was observed. Modifying the ratio of phage to chlamydiae altered the course of infection and affected phage replication. There was no evidence for the phage increasing the virulence of C. caviae infection.Over the last several years, four different phages of chlamydiae, in addition to a phage associated with Chlamydia psittaci isolated from an ornithosis infection in ducks over 25 years ago by Richmond and coworkers (22), have been described and characterized. Hsia et al. isolated phage CPG1 from in vitrocultured "Chlamydia caviae," the agent of guinea pig inclusion conjunctivitis (7,8). This was followed shortly thereafter by the isolation of phages Chp2 (2) and CPO1 (R.-C. Hsia and P. M. Bavoil, unpublished data) from Chlamydia abortus, AR39/ Cpn1 from Chlamydia pneumoniae (10, 18), and Chp3 from Chlamydia pecorum (3). The chlamydiaphages belong to a class of lytic phages that include the closely related Bdellovibrio bacteriovorus phage pMH2K (1) and the Spiroplasma melliferum phage SpV4 (21) and for which the single-stranded DNA coliphage X174 is the prototype (4). The chlamydial host range for the various chlamydiaphages is varied, but all are lytic for their respective hosts; however, it is interesting to note that chlamydiaphages have not yet been detected in association with Chlamydia trachomatis or Chlamydia muridarum.That five different chlamydiaphages have been described for chlamydiae infecting different animal species from geographically distinct areas would suggest that they are prevalent in chlamydiae in nature. Nevertheless, because all of the chlamydiaphages have been isolated from chlamydiae in tissue culture and their interaction with their hosts has been characterized from tissue culture, there is literally nothing known about the interaction of the chlamydiaphages with their bacterial hosts in the context of infection of the natural hosts of the bacteria. In fact, there are no data describing the interaction of any bacteriophage of an obligate intracellular bacterium in the natural animal host of the bacterium.It is indeed fortunate that ...

Recent advances in the understanding ofChlamydophila pecoruminfections, sixteen years after it was named as the fourth species of the Chlamydiaceae family

“…caviae infection delays the appearance of the peak level of Chlamydiae in animals and decreases the pathologic response [60]. …”

“…Although no evidence has been found for the integration of phage DNA into the Chlamydial chromosome [ 48 ], Chlamydiaphages could play a role in the pathogenesis of Chlamydia , since the presence of CPG1phage in C . caviae infection delays the appearance of the peak level of Chlamydiae in animals and decreases the pathologic response [ 60 ].…”

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

“…Chlamydiaphages are icosahedral single-stranded DNA (ssDNA) phages belonging to a subfamily of Microviridae termed Gokushovirinae (100). Chlamydiaphages are lytic to their hosts and might affect the infectivity and virulence of C. caviae (101) and delay RB replication and EB transitioning in C. abortus (102). The discovery of chlamydiaphages is exciting, and future investigation into the prevalence of chlamydiaphages among human chlamydial pathogens, their influence on disease outcomes, and their potential application to molecular genetic manipulation warrants further investigation.…”

Chlamydial plasmids and bacteriophages

“…Chlamydial phages can occur in the cell's cytosol, but most frequently bind to the cellular membrane of EB bodies, and are transferred in such a form together with chlamydia to other eukaryotic cells. In case of mixed intranasal infection with C. caviae and stock of phage φCPG1, a positive reaction in serum of Guinea pigs -high level of antibody to VP1 was observed (Rank et al, 2009).…”