Wu Shizhou, Wu Binjie, Liu Yunjie, Deng Shu, Lei Lei, Zhang Hui
Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
West China School of Public Health, Sichuan University, Chengdu, China.
Front Microbiol. 2022 Jun 14;13:936285. doi: 10.3389/fmicb.2022.936285. eCollection 2022.
Bone infection results in a complex inflammatory response and bone destruction. A broad spectrum of bacterial species has been involved for jaw osteomyelitis, hematogenous osteomyelitis, vertebral osteomyelitis or diabetes mellitus, such as (), coagulase-negative Staphylococcus species, and aerobic gram-negative bacilli. is the major pathogenic bacterium for osteomyelitis, which results in a complex inflammatory response and bone destruction. Although various antibiotics have been applied for bone infection, the emergence of drug resistance and biofilm formation significantly decrease the effectiveness of those agents. In combination with gram-positive aerobes, gram-negative aerobes and anaerobes functionally equivalent pathogroups interact synergistically, developing as pathogenic biofilms and causing recurrent infections. The adhesion of biofilms to bone promotes bone destruction and protects bacteria from antimicrobial agent stress and host immune system infiltration. Moreover, bone is characterized by low permeability and reduced blood flow, further hindering the therapeutic effect for bone infections. To minimize systemic toxicity and enhance antibacterial effectiveness, therapeutic strategies targeting on biofilm and bone infection can serve as a promising modality. Herein, we focus on biofilm and bone infection eradication with targeting therapeutic strategies. We summarize recent targeting moieties on biofilm and bone infection with peptide-, nucleic acid-, bacteriophage-, CaP- and turnover homeostasis-based strategies. The antibacterial and antibiofilm mechanisms of those therapeutic strategies include increasing antibacterial agents' accumulation by bone specific affinity, specific recognition of phage-bacteria, inhibition biofilm formation in transcription level. As chronic inflammation induced by infection can trigger osteoclast activation and inhibit osteoblast functioning, we additionally expand the potential applications of turnover homeostasis-based therapeutic strategies on biofilm or infection related immunity homeostasis for host-bacteria. Based on this review, we expect to provide useful insights of targeting therapeutic efficacy for biofilm and bone infection eradication.
骨感染会引发复杂的炎症反应和骨质破坏。多种细菌种类都与颌骨骨髓炎、血源性骨髓炎、脊椎骨髓炎或糖尿病相关，比如（）、凝固酶阴性葡萄球菌属以及需氧革兰氏阴性杆菌。金黄色葡萄球菌是骨髓炎的主要致病菌，会导致复杂的炎症反应和骨质破坏。尽管各种抗生素已被用于治疗骨感染，但耐药性的出现和生物膜的形成显著降低了这些药物的疗效。革兰氏阳性需氧菌、革兰氏阴性需氧菌和厌氧菌等功能等效的病原体群相互协同作用，形成致病性生物膜并导致反复感染。生物膜与骨的黏附会促进骨质破坏，并保护细菌免受抗菌药物压力和宿主免疫系统浸润的影响。此外，骨的特点是通透性低和血流减少，这进一步阻碍了对骨感染的治疗效果。为了将全身毒性降至最低并提高抗菌效果，针对生物膜和骨感染的治疗策略可能是一种有前景的方式。在此，我们聚焦于通过靶向治疗策略根除生物膜和骨感染。我们总结了基于肽、核酸、噬菌体、磷酸钙和周转稳态的策略在生物膜和骨感染方面的最新靶向部分。这些治疗策略的抗菌和抗生物膜机制包括通过骨特异性亲和力增加抗菌药物的积累、噬菌体与细菌的特异性识别、在转录水平抑制生物膜形成。由于感染引起的慢性炎症会触发破骨细胞活化并抑制成骨细胞功能，我们还扩展了基于周转稳态的治疗策略在生物膜或感染相关宿主-细菌免疫稳态方面的潜在应用。基于这篇综述，我们期望能为根除生物膜和骨感染的靶向治疗效果提供有用的见解。
