Various bacteria can cause human diseases. They spread directly from person to person or indirectly via various environmental matrixes, such as food and water. Major foodand waterborne pathogens include Campylobacter, Listeria, Salmonella, Shigella, Shiga toxin-producing Escherichia coli, Salmonella, Yersinia, and Vibrio (31). Most of these pathogens spread through the fecal-oral route. Their primary hosts include humans, farm animals (e.g., cows, pigs, and chickens), and wildlife (e.g., deer, birds). These hosts contribute to the spread of pathogens. For example, geese and other birds are known to harbor diverse Campylobacter (29, 40, 59) and Salmonella spp. (40). However, some of these pathogens also survive for long periods of time and even grow in environments such as water, soil, sediment, and algae (13, 22, 32), in many cases in association with or by forming biofilms (35, 36, 52). Since difficulties are associated with detecting various pathogens in a timely manner, the microbial quality of food and water has been monitored using so-called fecal indicator bacteria (FIB), such as E. coli and enterococci (22, 24). Although their primary habitats are the gastrointestinal tracts of warmblooded animals (18, 49), some FIB strains are more adapted to soil or other environments (22, 24, 37). Moreover, alternative FIB, such as Bacteroides, have been used to identify the occurrence of pathogens and their potential sources of contamination (28, 59). However, poor correlations have been reported between pathogen and FIB concentrations (23, 58), which limits the use of FIB for predicting the occurrence of pathogens. Some opportunistic pathogens, including Mycobacterium avium and Legionella pneumophila, are not of a fecal origin. These opportunistic pathogens use environments such as water distribution systems (11, 14, 15) and showerhead biofilms (12) as their primary habitats, and occasionally infect humans to cause diseases. Furthermore, various environmental bacteria have been reported as emerging pathogens. Among these, Arcobacter spp. are of great interest because this genus is frequently and abundantly detected in many wastewater treatment plants (10, 50). This genus is phylogenetically closely related to Campylobacter, but is metabolically more versatile and can grow at relatively low temperatures and with a wider range of O2 concentrations (9). Some members of Arcobacter have also been reported to form symbiotic relationships with protists (16). A better understanding of the ecology of these environmental pathogens is essential for preventing their occurrence and spread (39, 47). Antibiotics are one of the most important scientific discoveries to combat pathogens. Antibiotic treatments save millions of lives each year worldwide. However, nearly a century of antibiotic use and misuse has resulted in the evolution of the resistance of bacterial pathogens to most antibiotics approved for medical use (56). In addition to clinical settings, antibiotic resistance is an issue in environments. Raw sewage is one of the major reservoirs of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) (45). Farm animals, including cows, pigs, and horses, can also harbor various ARB, some of which are pathogenic to humans (8, 33, 55). These ARB/ARGs contaminate surrounding and downstream environments (3, 30). Wildlife can also contribute to the spread of ARB/ARGs. Migratory birds are most likely responsible for the spread of ARB/ARGs to wide areas, including remote Arctic islands (34) and Antarctica (48). Horizontal gene transfer (HGT) plays an important role in the spread of ARGs among diverse bacteria (4, 44). Some ARGs are found on mobile genetic elements, such as insertion sequences and transposons, and can be transferred between cells when mediated by plasmids, integrative conjugative elements (ICEs), or bacteriophages (44). The HGT of ARGs can occur in environments such as wastewater treatment plants (45). In addition to conjugation (mediated by plasmids and ICEs) and transduction (mediated by bacteriophages), ARGs can be transferred between cells via extracellular vesicles (6, 53, 54) as well as when bacteria take up naked DNA (i.e., transformation). A recent study demonstrated that the grazing activities of Ciliates enhanced the release of ARGs from bacterial cells into the environment (5). These naked ARGs can be taken up by bacteria, thereby transforming them to be resistant to antibiotics. To prevent the spread of ARB/ ARGs, it is necessary to understand the mechanisms and frequencies of ARG acquisition in environments. The major challenges associated with the study of pathogens and ARB/ARGs in environments include (i) various types of targets, (ii) low concentrations, (iii) intra-species diversity, (iv) previously uncharacterized target genes, and (v) the occurrence of HGT. However, we can see great opportunities in these challenges. Recent technological advances have provided various tools to explore these opportunities. Three notable tools are briefly summarized below.

中文翻译：

---

环境中病原体和抗生素耐药菌的生态学：挑战与机遇

各种细菌都能引起人类疾病。它们直接在人与人之间传播，或通过各种环境基质（例如食物和水）间接传播。主要的食物和水传播病原体包括弯曲杆菌、李斯特菌、沙门氏菌、志贺氏菌、产志贺毒素大肠杆菌、沙门氏菌、耶尔森氏菌和弧菌 (31)。大多数这些病原体通过粪口途径传播。它们的主要宿主包括人类、农场动物（例如牛、猪和鸡）和野生动物（例如鹿、鸟）。这些宿主有助于病原体的传播。例如，已知鹅和其他鸟类携带多种弯曲杆菌 (29, 40, 59) 和沙门氏菌属。(40)。然而，其中一些病原体也能存活很长时间，甚至在水、土壤、沉积物和藻类等环境中生长 (13, 22, 32)，在许多情况下，与生物膜有关或通过形成生物膜 (35, 36, 52)。由于难以及时检测各种病原体，因此已使用所谓的粪便指示菌 (FIB)，例如大肠杆菌和肠球菌 (22, 24) 来监测食物和水的微生物质量。尽管它们的主要栖息地是温血动物的胃肠道 (18, 49)，但一些 FIB 菌株更适应土壤或其他环境 (22, 24, 37)。此外，替代 FIB，如拟杆菌，已被用于识别病原体的发生及其潜在的污染源 (28, 59)。然而，据报道病原体和 FIB 浓度之间的相关性较差 (23, 58)，这限制了 FIB 用于预测病原体发生的用途。一些机会性病原体，包括鸟分枝杆菌和嗜肺军团菌，都不是粪便来源。这些机会性病原体利用供水系统（11、14、15）和淋浴喷头生物膜（12）等环境作为其主要栖息地，偶尔会感染人类引起疾病。此外，各种环境细菌已被报道为新出现的病原体。其中，Arcobacter spp。非常有趣，因为在许多污水处理厂中经常和大量检测到该属 (10, 50)。该属在系统发育上与弯曲杆菌密切相关，但在代谢上更通用，可以在相对较低的温度和更宽的 O2 浓度范围内生长 (9)。据报道，Arcobacter 的一些成员与原生生物形成共生关系 (16)。更好地了解这些环境病原体的生态学对于防止它们的发生和传播至关重要 (39, 47)。抗生素是对抗病原体最重要的科学发现之一。抗生素治疗每年在全世界挽救数百万人的生命。然而，近一个世纪的抗生素使用和滥用导致细菌病原体对大多数批准用于医疗用途的抗生素产生耐药性（56）。除了临床环境外，抗生素耐药性也是环境中的一个问题。未经处理的污水是抗生素抗性细菌 (ARB) 和抗生素抗性基因 (ARG) 的主要储存库之一 (45)。农场动物，包括奶牛、猪和马，也可能携带各种 ARB，其中一些对人类具有致病性 (8, 33, 55)。这些 ARB/ARG 会污染周围和下游环境 (3, 30)。野生动物也会促进 ARB/ARG 的传播。候鸟最有可能将 ARB/ARGs 传播到广大地区，包括偏远的北极岛屿 (34) 和南极洲 (48)。水平基因转移 (HGT) 在 ARG 在不同细菌中的传播中起着重要作用 (4, 44)。一些 ARG 存在于可移动的遗传元件上，例如插入序列和转座子，当由质粒、整合接合元件 (ICE) 或噬菌体介导时，可以在细胞之间转移 (44)。ARG 的 HGT 可能发生在污水处理厂等环境中 (45)。除了结合（由质粒和 ICE 介导）和转导（由噬菌体介导），ARGs 可以通过细胞外囊泡 (6, 53, 54) 以及当细菌吸收裸 DNA（即转化）在细胞之间转移。最近的一项研究表明，纤毛虫的放牧活动增强了 ARG 从细菌细胞释放到环境中 (5)。这些裸露的 ARG 可以被细菌吸收，从而将它们转化为对抗生素具有抗性。为了防止 ARB/ARG 的传播，有必要了解环境中 ARG 获取的机制和频率。与环境中病原体和 ARB/ARG 研究相关的主要挑战包括 (i) 各种类型的目标，(ii) 低浓度，(iii) 种内多样性，(iv) 以前未表征的目标基因，以及 (v) HGT的发生。然而，我们可以在这些挑战中看到巨大的机遇。最近的技术进步为探索这些机会提供了各种工具。下面简要总结了三个值得注意的工具。