**6. Antibiotic resistance in Chlamydiae**

There are few reports documenting antibiotic resistance in Chlamydiae. Furthermore, there are no examples of natural or permanent antibiotic resistance in strains that cause disease in humans. In some strains, the detected antibiotic resistance cannot be identified in vitro, which hinders the recognition and interpretation of antibiotic resistance. This is due to differences in laboratory procedures for chlamydial culture, low recovery rates of clinical isolates, and the unknown significance of heterotypic resistance observed in culture [4]. Although antibiotic resistance in Chlamydiae has not been reported throughout history, a few reports indicate that they have the ability to develop resistant phenotypes to a significant extent. In vitro antibiotic resistance in Chlamydiae is demonstrated by contemporary examples of mutagenesis, recombination, and genetic transformation. In addition, tetra-cycloneresistant *Chlamydia* strains can be isolated from pigs, producing tetra-cycline-resistant genes under extreme pressure [17].

In *Chlamydia* infections without any complex infections present, tetracyclines (TETs) and azithromycin (AZM) are commonly used as they are highly effective in treating these diseases [8]. However, data obtained so far indicate that *Chlamydia* may develop long-term infections that are resistant to antibiotic treatment and involve persistence in the reproductive cycle of the microorganism, leading to a deterioration of the infection. Further data is required to confirm these descriptions [10].

Antibiotic treatment may fail due to the development of chlamydial persistence in laboratory studies, where the infection can become unresponsive to antibiotics. The use of penicillin, in particular, can trigger this persistence, which hinders the differentiation of reticulate bodies into elementary bodies and interrupts cell division [15]. Distinguishing between persistence or phenotypic resistance and antibiotic resistance is a difficult task. However, in vivo evidence suggests that persistence is a common occurrence, with the presence of chlamydial RNA, DNA, and abnormal reticulate bodies often found in culture-negative cases [1].

In *Chlamydia*, there is no one-size-fits-all method to test for antibiotic resistance. The accuracy of antibiotic susceptibility analysis can be affected by several factors, including the type of cell lines utilized, the passage number of both the host cells and *Chlamydia*, the size of the inoculum, and the time at which antibiotics are added. In

#### *Chlamydias as a Zooonosis and Antibiotic Resistance in Chlamydiae DOI: http://dx.doi.org/10.5772/intechopen.110599*

addition, due to the bacteria's fastidious nature, the success rate of isolating clinical samples for culture-based diagnostic methods can vary, making them less favorable when compared to nucleic acid amplification tests with high sensitivity [17].

Stable strains of *C. suis* that are resistant to tetracycline have been discovered in the United States and Italy. Researchers have identified seven isolates that contain genomic islands of varying lengths and compositions. These genomic islands encode a tetracycline efflux pump called tet(C) and a novel insertion sequence element that likely helps integrate the genomic islands into the chlamydial genome at specific sites [17].

Growing *Chlamydia* bacteria in conditions with sub-inhibitory or excessively high concentrations of six different types of antibiotics can encourage the development of mutations and genetic resistance in various *Chlamydia* strains. Some spontaneously occurring mutations that cause resistance have minimal impact on the chlamydial growth characteristics, while others may cause competitive disadvantages in resistant strains [6].

A technique was developed to facilitate the transfer of genes in the laboratory by using chlamydial strains with mutations that make them resistant to antibiotics and infecting them simultaneously with tetracycline-resistant *C. suis* strains. This process, which involves introducing dissimilar antibiotic-resistant markers into co-infecting strains, can cause genetic exchange between different species of *Chlamydia* and result in genomic rearrangement and mosaicism. Researchers demonstrated the first successful transformation of *Chlamydia*, both naturally and using electroporation, by introducing spontaneous mutations that conferred aminoglycoside resistance. However, significant limitations are still associated with the techniques used for *Chlamydia* recombination and transformation [17].
