Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, Oklahoma, USA.
mBio. 2023 Apr 25;14(2):e0046423. doi: 10.1128/mbio.00464-23. Epub 2023 Apr 3.
Moraxella catarrhalis is found almost exclusively within the human respiratory tract. This pathobiont is associated with ear infections and the development of respiratory illnesses, including allergies and asthma. Given the limited ecological distribution of M. catarrhalis, we hypothesized that we could leverage the nasal microbiomes of healthy children without M. catarrhalis to identify bacteria that may represent potential sources of therapeutics. was more abundant in the noses of healthy children compared to children with cold symptoms and M. catarrhalis. We cultured from nasal samples and determined that most isolates of Rothia dentocariosa and "Rothia similmucilaginosa" were able to fully inhibit the growth of M. catarrhalis , whereas isolates of Rothia aeria varied in their ability to inhibit M. catarrhalis. Using comparative genomics and proteomics, we identified a putative peptidoglycan hydrolase called ecreted ntien (SagA). This protein was present at higher relative abundance in the secreted proteomes of and than in those from non-inhibitory , suggesting that it may be involved in M. catarrhalis inhibition. We produced SagA from in Escherichia coli and confirmed its ability to degrade M. catarrhalis peptidoglycan and inhibit its growth. We then demonstrated that and reduced M. catarrhalis levels in an air-liquid interface culture model of the respiratory epithelium. Together, our results suggest that restricts M. catarrhalis colonization of the human respiratory tract . Moraxella catarrhalis is a pathobiont of the respiratory tract, responsible for ear infections in children and wheezing illnesses in children and adults with chronic respiratory diseases. Detection of M. catarrhalis during wheezing episodes in early life is associated with the development of persistent asthma. There are currently no effective vaccines for M. catarrhalis, and most clinical isolates are resistant to the commonly prescribed antibiotics amoxicillin and penicillin. Given the limited niche of M. catarrhalis, we hypothesized that other nasal bacteria have evolved mechanisms to compete against M. catarrhalis. We found that are associated with the nasal microbiomes of healthy children without Next, we demonstrated that inhibit M. catarrhalis and on airway cells. We identified an enzyme produced by called SagA that degrades M. catarrhalis peptidoglycan and inhibits its growth. We suggest that or SagA could be developed as highly specific therapeutics against M. catarrhalis.
卡他莫拉菌几乎只存在于人类的呼吸道中。这种条件致病菌与耳部感染和呼吸道疾病的发展有关，包括过敏和哮喘。鉴于卡他莫拉菌的生态分布有限，我们假设可以利用没有卡他莫拉菌的健康儿童的鼻腔微生物组来鉴定可能成为治疗药物潜在来源的细菌。 Rothia dentocariosa 在健康儿童的鼻腔中比有感冒症状和卡他莫拉菌的儿童更为丰富。我们从鼻腔样本中培养 Rothia dentocariosa，并确定大多数 Rothia dentocariosa 和“Rothia similmucilaginosa”的分离株能够完全抑制卡他莫拉菌的生长，而 Rothia aeria 的分离株抑制卡他莫拉菌的能力则有所不同。使用比较基因组学和蛋白质组学，我们鉴定出一种名为 SagA 的假定肽聚糖水解酶。该蛋白在 Rothia dentocariosa 和 Rothia similmucilaginosa 的分泌蛋白组中的相对丰度较高，而在非抑制性蛋白中的丰度较低，表明它可能参与了卡他莫拉菌的抑制。我们从 Escherichia coli 中产生 SagA，并证实其能够降解卡他莫拉菌的肽聚糖并抑制其生长。然后，我们证明 Rothia dentocariosa 和 Rothia similmucilaginosa 在呼吸道上皮的气液界面培养模型中降低了卡他莫拉菌的水平。总之，我们的结果表明，Rothia dentocariosa 和 Rothia similmucilaginosa 限制了卡他莫拉菌在人类呼吸道中的定植。卡他莫拉菌是呼吸道的条件致病菌，可导致儿童耳部感染和患有慢性呼吸道疾病的儿童和成人喘息性疾病。在生命早期喘息发作期间检测到卡他莫拉菌与持续性哮喘的发展有关。目前尚无针对卡他莫拉菌的有效疫苗，大多数临床分离株对常用抗生素阿莫西林和青霉素耐药。鉴于卡他莫拉菌的生态位有限，我们假设其他鼻腔细菌已经进化出与卡他莫拉菌竞争的机制。我们发现 Rothia dentocariosa 与没有卡他莫拉菌的健康儿童的鼻腔微生物组有关。接下来，我们证明 Rothia dentocariosa 和 Rothia similmucilaginosa 抑制卡他莫拉菌在气道细胞上的生长。我们鉴定出一种由 Rothia dentocariosa 产生的名为 SagA 的酶，该酶可降解卡他莫拉菌的肽聚糖并抑制其生长。我们建议可以将 Rothia dentocariosa 或 SagA 开发为针对卡他莫拉菌的高度特异性治疗药物。
