Systematic investigation of the emerging pathogen of Tsukamurella species in a Chinese tertiary teaching hospital

Abstract

Tsukamurella species have been clinically regarded as rare but emerging opportunistic pathogens causing various infections in humans. Tsukamurella pneumonia has often been misdiagnosed as pulmonary tuberculosis due to its clinical presentation resembling tuberculosis-like syndromes. Tsukamurella species have also been confused in the laboratory with other phylogenetic bacteria, such as Gordonia . This study aimed to investigate the clinical, microbiological, and molecular characteristics; species distribution; and antimicrobial susceptibility of Tsukamurella species. Immunodeficiency and chronic pulmonary disease appeared to be risk factors for Tsukamurella pneumonia, and the presence of bronchiectasis and pulmonary nodules on imaging was highly correlated with this infection. The study confirmed that groEL (heat shock protein 60) and secA (the secretion ATPase) genes are reliable for identifying Tsukamurella species. Additionally, the ssrA (stable small RNA) gene showed promise as a tool for discriminating between different Tsukamurella species with the shortest sequence length. In terms of antimicrobial susceptibility, quinolones, trimethoprim/sulfamethoxazole, amikacin, minocycline, linezolid, and tigecycline demonstrated potent in vitro activity against Tsukamurella isolates in our study. The study also proposed a resistance mechanism involving a substitution (S91R) within the quinolone-resistance-determining region of the gyrA gene, which confers resistance to levofloxacin and ciprofloxacin. Furthermore, we found that disk diffusion testing is not suitable for testing the susceptibilities of Tsukamurella isolates to ciprofloxacin, imipenem, and minocycline. In conclusion, our systematic investigation may contribute to a better understanding of this rare pathogen. IMPORTANCE Tsukamurella species are rare but emerging human pathogens that share remarkable similarities with other mycolic acid–containing genera of the order Actinomycetales, especially Mycobacterium tuberculosis . Consequently, misdiagnosis and therapeutic failures can occur in clinical settings. Despite the significance of accurate identification, antimicrobial susceptibility, and understanding the resistance mechanism of this important genus, our knowledge in these areas remains fragmentary and incomplete. In this study, we aimed to address these gaps by investigating promising identification methods, the antimicrobial susceptibility patterns, and a novel quinolone resistance mechanism in Tsukamurella species, utilizing a collection of clinical isolates. The findings of our study will contribute to improve diagnosis and successful management of infections caused by Tsukamurella species, as well as establishing well-defined performance and interpretive criteria for antimicrobial susceptibility testing.

A Case Report of a Rare Pulmonary Opportunistic Infection in an Infant Caused by Tsukamurella tyrosinosolvens

“… 8 Sequencing of 16S ribosomal RNA (16S rRNA), the essential secretory protein-encoding gene secA (the secretion ATPase), rpoB (beta-subunit of DNA-dependent RNA polymerase), groEL (60 kDa chaperonin and heat shock protein), and the transfer messenger RNA coding gene ssrA (stable small RNA) can be used to assist in the rapid and reliable identification of Tsukamura species. 4 Metagenomic next-generation sequencing (mNGS) as a new type of pathogen detection method in the complicated and plays an important role in a rare infectious diseases. The mNGS sequencing can also be considered if conditions permit, which can comprehensively analyze the pathogens in vivo and improve the diagnostic rate.…”

“…According to a recent drug susceptibility study of multiple strains of Tsukamurella species, Tsukamurella species isolates in vitro showed high sensitivity to quinolones, trimethoprim/sulfamethoxazole, amikacin, minocycline, linezolid, and tigecycline. 4 …”

“…MALDI-TOF MS compared with 16S rRNA, time and cost advantages, but can only be identified to species level, and there is a certain error detection rate. 4 Unfortunately, despite active treatments, such as anti-infection, immune regulation with gamma globulin, methylprednisolone pulse therapy, intravenous nutritional support, and invasive ventilator-assisted ventilation, the patient’s family required abandonment of treatment due to her critical condition and threatened life. The patient was discharged with a stomach tube during the third month of hospitalization.…”