Characterization of a New CAMP Factor Carried by an Integrative and Conjugative Element in Streptococcus agalactiae and Spreading in Streptococci

Genetic exchanges between Streptococci occur frequently and contribute to their genome diversification. Most of sequenced streptococcal genomes carry multiple mobile genetic elements including Integrative and Conjugative Elements (ICEs) that play a major role in these horizontal gene transfers. In addition to genes involved in their mobility and regulation, ICEs also carry genes that can confer selective advantages to bacteria. Numerous elements have been described in S. agalactiae especially those integrated at the 3′ end of a tRNALys encoding gene. In strain 515 of S. agalactiae, an invasive neonate human pathogen, the ICE (called 515_tRNALys) is functional and carries different putative virulence genes including one encoding a putative new CAMP factor in addition to the one previously described. This work demonstrated the functionality of this CAMP factor (CAMP factor II) in Lactococcus lactis but also in pathogenic strains of veterinary origin. The search for co-hemolytic factors in a collection of field strains revealed their presence in S. uberis, S. dysgalactiae, but also for the first time in S. equisimilis and S. bovis. Sequencing of these genes revealed the prevalence of a species-specific factor in S. uberis strains (Uberis factor) and the presence of a CAMP factor II encoding gene in S. bovis and S. equisimilis. Furthermore, most of the CAMP factor II positive strains also carried an element integrated in the tRNALys gene. This work thus describes a CAMP factor that is carried by a mobile genetic element and has spread to different streptococcal species.

链球菌属细菌间的遗传交换事件频发，是其基因组多样化的重要驱动因素。目前已测序的链球菌基因组中，多数携带多种可移动遗传元件，其中整合接合元件（Integrative and Conjugative Elements，ICEs）在这类水平基因转移过程中扮演核心角色。整合接合元件除编码自身移动与调控相关基因外，还可携带赋予细菌选择优势的功能基因。无乳链球菌（Streptococcus agalactiae，S. agalactiae）中已报道存在多种此类元件，其中尤以整合于赖氨酸转运RNA（tRNALys）编码基因3'端的元件最为常见。在作为人类新生儿侵袭性致病菌的无乳链球菌515菌株内，存在一种命名为515_tRNALys的功能性整合接合元件，该元件除携带已报道的基因外，还包含多个潜在毒力基因，其中就包括一个编码新型CAMP因子（CAMP factor）的候选基因。本研究证实，该CAMP因子（即CAMP因子II）在乳酸乳球菌（Lactococcus lactis）以及兽源致病菌株中均具有功能活性。通过对一批野外分离菌株的协同溶血因子进行筛查发现，此类因子不仅见于乳房链球菌（Streptococcus uberis，S. uberis）、停乳链球菌（Streptococcus dysgalactiae，S. dysgalactiae），还首次在似马链球菌（Streptococcus equisimilis，S. equisimilis）与牛链球菌（Streptococcus bovis，S. bovis）中被检出。对上述基因进行测序分析后发现，乳房链球菌菌株中普遍存在一种物种特异性因子（将其命名为Uberis因子），而牛链球菌与似马链球菌则携带CAMP因子II编码基因。此外，绝大多数携带CAMP因子II的菌株，其基因组内均存在整合于tRNALys基因的可移动遗传元件。综上，本研究报道了一种由可移动遗传元件携带、并已在不同链球菌属物种间传播的CAMP因子。