The chlamydiae are common pathogens of humans and animals. Chlamydia trachomatis causes blinding trachoma and severe reproductive complications in humans. More than 100 million cases of chlamydial genital infection and >40 million cases of trachoma occur worldwide every year. C. pneumoniae is a common cause of atypical pneumonia in humans, with >50% of adults being exposed. C. suis, C. psittaci, C. pecorum, and C. abortus all cause economically-important livestock infections. Chlamydial infections in humans and domestic animals are typically controlled using either macrolide (usually azithromycin [AZM]) or tetracycline (tetracycline [TET] and doxycycline [DOX]) treatment. TET-containing feed has also been used to limit chlamydial infections in livestock, particularly in pig meat production, though its use is viewed critically due to the emergence of C. suis strains carrying tetracycline resistance genes (TetR). Given recent observations that TetR can be horizontally transferred from C. suis to human clinical strains of C. trachomatis during co-culture, there is significant concern that such an event could also occur in nature. Fortunately, TetR-carrying C. trachomatis clinical strains have not yet been observed.
Published data suggest that treatment failure rate during human chlamydial infections ranges from 8-23%. Multiple mechanisms have been proposed for such failures, including: i) development of heterotypic antibiotic resistance due to slower growth in non-optimal environments and/or entry into stress-induced developmental cycle arrest; and ii) infection of anatomic sites where chlamydiae are protected from antibiotics. Recent work has provided compelling data that AZM anti-chlamydial activity is reduced in hypoxic conditions, as well as when the chlamydiae enter a reversible, non-replicating but viable developmental state. Finally, animal model experiments have determined that the GI tract may be an antibiotic protected anatomical site, which serves as a reservoir for re-establishment of genital infection post-antibiotic treatment.
Though chlamydial biology has become increasingly understood over the last 30 years, the number of effective anti-chlamydials has remained essentially unchanged. Furthermore, sustained AZM therapy has been associated with adverse cardiovascular outcomes in patients, raising the possibility that increasing AZM doses to eliminate GI carriage might be contraindicated. Emergence of stable homotypic antibiotic resistance in human chlamydial species also remains a threat. Thus, development of novel anti-chlamydials remains a high priority. Recently identified candidates include bacterial type III secretion inhibitors, chlamydial enzyme inhibitors, and antagonists of host cell functions essential to chlamydial development. We also expect that identification of new anti-chlamydials will be hastened by the recent development of methods to engineer targeted gene deletions in the chlamydiae. This Research Topic will highlight development of new anti-chlamydial approaches by including original research and review papers that investigate: i) new chlamydial or host cellular drug targets identified using biochemical or by genetic methods; ii) novel methods for identifying potential drug targets; iii) inhibitors of infection or development that target chlamydial or host cell genes; iv) non-chemical methods to inhibit chlamydial development or inactivate the organism; v) treatment failure in humans or animals; and vi) identification and/or characterization of mechanisms that allow chlamydiae to escape antimicrobial effects in culture or in vivo.
The chlamydiae are common pathogens of humans and animals. Chlamydia trachomatis causes blinding trachoma and severe reproductive complications in humans. More than 100 million cases of chlamydial genital infection and >40 million cases of trachoma occur worldwide every year. C. pneumoniae is a common cause of atypical pneumonia in humans, with >50% of adults being exposed. C. suis, C. psittaci, C. pecorum, and C. abortus all cause economically-important livestock infections. Chlamydial infections in humans and domestic animals are typically controlled using either macrolide (usually azithromycin [AZM]) or tetracycline (tetracycline [TET] and doxycycline [DOX]) treatment. TET-containing feed has also been used to limit chlamydial infections in livestock, particularly in pig meat production, though its use is viewed critically due to the emergence of C. suis strains carrying tetracycline resistance genes (TetR). Given recent observations that TetR can be horizontally transferred from C. suis to human clinical strains of C. trachomatis during co-culture, there is significant concern that such an event could also occur in nature. Fortunately, TetR-carrying C. trachomatis clinical strains have not yet been observed.
Published data suggest that treatment failure rate during human chlamydial infections ranges from 8-23%. Multiple mechanisms have been proposed for such failures, including: i) development of heterotypic antibiotic resistance due to slower growth in non-optimal environments and/or entry into stress-induced developmental cycle arrest; and ii) infection of anatomic sites where chlamydiae are protected from antibiotics. Recent work has provided compelling data that AZM anti-chlamydial activity is reduced in hypoxic conditions, as well as when the chlamydiae enter a reversible, non-replicating but viable developmental state. Finally, animal model experiments have determined that the GI tract may be an antibiotic protected anatomical site, which serves as a reservoir for re-establishment of genital infection post-antibiotic treatment.
Though chlamydial biology has become increasingly understood over the last 30 years, the number of effective anti-chlamydials has remained essentially unchanged. Furthermore, sustained AZM therapy has been associated with adverse cardiovascular outcomes in patients, raising the possibility that increasing AZM doses to eliminate GI carriage might be contraindicated. Emergence of stable homotypic antibiotic resistance in human chlamydial species also remains a threat. Thus, development of novel anti-chlamydials remains a high priority. Recently identified candidates include bacterial type III secretion inhibitors, chlamydial enzyme inhibitors, and antagonists of host cell functions essential to chlamydial development. We also expect that identification of new anti-chlamydials will be hastened by the recent development of methods to engineer targeted gene deletions in the chlamydiae. This Research Topic will highlight development of new anti-chlamydial approaches by including original research and review papers that investigate: i) new chlamydial or host cellular drug targets identified using biochemical or by genetic methods; ii) novel methods for identifying potential drug targets; iii) inhibitors of infection or development that target chlamydial or host cell genes; iv) non-chemical methods to inhibit chlamydial development or inactivate the organism; v) treatment failure in humans or animals; and vi) identification and/or characterization of mechanisms that allow chlamydiae to escape antimicrobial effects in culture or in vivo.
