Enhancing the diagnosis accuracy of Chlamydia psittaci infection via metagenomic next-generation sequencing

Metagenomic next-generation sequencing (mNGS) is an innovative diagnostic technique that integrates high-throughput sequencing with bioinformatics analysis. Recently, its unbiased approach, broad pathogen coverage, and rapid turnaround have led to its expanded use in diagnosing infectious diseases. This is particularly true for atypical bacterial pathogens such as Chlamydia psittaci , Chlamydia pneumoniae , Mycoplasma pneumoniae , and Legionella spp., for which mNGS has demonstrated significant diagnostic utility. C. psittaci , a highly pathogenic obligate intracellular bacterium, can cause severe community-acquired pneumonia (CAP). Its virulence is attributed to unique genomic pathogenicity islands, which encode both a specialized secretion system (such as the Type III Secretion System) and effector proteins like the Chlamydial Protease-like Activity Factor (CPAF), coupled with its capacity for rapid intracellular replication. Furthermore, its close genetic similarity to C. pneumoniae complicates differentiation by standard Polymerase Chain Reaction (PCR) assays. This review examines the advancements in using mNGS to diagnose C. psittaci infections in clinical settings and discusses the remaining challenges. The excessive use of antibiotics in clinical practice is still a common problem. Through its unbiased detection, mNGS can accurately identify mixed infections, thereby providing a microbiological basis for targeted antibiotic therapy. Our compilation of case reports and studies from the last five years indicates that mNGS effectively assists clinicians in promptly adjusting antibiotic regimens and holds great potential for the clinical identification of chlamydial co-infections. • mNGS comprehensively reviews diagnosis of C. psittaci , an atypical pneumonia pathogen. • Unbiased mNGS detects C. psittaci and discriminates it from genetically similar Chlamydia spp. • mNGS accurately identifies mixed infections, enabling targeted antibiotic therapy and stewardship. • Clinical cases show mNGS supports timely antibiotic adjustments, improving patient management. • Discusses current challenges and future potential of mNGS in psittacosis and chlamydial co-infections.