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養鶏産業とヒトにおける広域スペクトラムセファロスポリン耐性サルモネラの汚染実態および伝播に関する研究

重村, 洋明 岐阜大学

2022.03.14

概要

世界保健機関は,ヒトの重篤な細菌感染の治療に使用し、ヒト以外からヒトに感染する可能性のある細菌による感染症の治療に使用するような抗菌剤を,医療上の最重要抗菌剤と位置付けており、第 3 世代セファロスポリン等の広城スペクトラムセファロスポリン(ESC) を,最重要抗菌剤の1つに挙げている。そのため,ESC 耐性菌の制御は,公衆衛生上重要な課題となっている。特に,小児のサルモネラ症の治療には,ESC が選択されるため,ESC 耐性サルモネラの出現,拡散はサルモネラ症の治療において大きな弊害となる。本研究は,ESC 耐性サルモネラの汚染状況およびESC 耐性を付与するβ-ラクタマーゼ遺伝子(bla遺伝子)の拡散に関する因子を明らかにすることを目的とした。

第一章では、市販鶏肉における ESC 耐性サルモネラの汚染状況を明らかにするため, 2011年から2015年に福岡県の市販鶏肉から分離されたサルモネラ菌株について,ESC 耐性株を検索し,23.6%(25/106 株)が ESC 耐性株であったことを明らかにした。また,養鶏業界におけるセフチオフルの適応外使用と ESC 耐性株との関係を明らかにするため、各年のサルモネラ分離菌株に占める ESC 耐性株の割合の年次推移を過去の調査結果と比較した。これにより,2004年の0%(0/13株)から2011年の45.5%(10/22株)まで増加したが,2012年以降減少し,2015年には10.5%(2/19株)となったことを示した。この割合の減少は,b/aow-2を保持するレプリコンタイプ不明プラスミド保有サルモネラの減少に起因するものであった。また,ESC 耐性株の割合の推移は,2012年3月の国内養鶏業界におけるセフチオフルの使用自粛と関連していることを示唆した。

第二章では,日本国内の採卵鶏生産および鶏卵・液卵加エチェーン(LB-EP チェーン)におけるESC 耐性サルモネラの汚染状況を明らかにするため,2014年を除く 2009年から2016年における国内のLB-EP チェーンで分離されたサルモネラ菌株について,ESC 耐性株を検索し,分離株の6.7% (15/224株)がESC 耐性株であったことを明らかにした。また,同一の採卵鶏生産チェーンの育雛場や卵殻に由来する Salmonella enterica serovar Chioがblao-2を含む複数の薬剤耐性遺伝子,ISEcplおよび IS26を保持するIncA/C」型プラスミドを保有していた。さらに,これら IncA/C;型プラスミドの一部または全体(あるいは広範囲)を染色体に組込んだ S. Ohio に加え、blacenx-1-1保持プラスミドの一部を染色体に組込んだ S. Cerro が確認された。これらサルモネラにおいて、染色体への組込みによるbla 遺伝子には ISEcplが,また bla遺伝子を含む複数の薬剤耐性遺伝子の獲得に IS26が関与していた。このことから,bla遺伝子を含む薬剤耐性遺伝子の拡散には,プラスミドだけでなく,プラスミド上に存在する ISEcplや IS26による転移も関与していることが示唆された。

第三章では,日本国内の食品従事者のサルモネラ保菌率および ESC 耐性サルモネラの保菌状況を明らかにするため,2017年の飲食店の調理従事者・給仕者,食品加工者等の食品従事者のサルモネラの保菌率を調査し、サルモネラ分離株について,ESC 耐性株を検索した。日本国内の食品従事者の0.11%(164/145,220検体)が、サルモネラを保菌していることを明らかにした。また,食品従事者から分離された 158株について調査したところ,4.4%(7/158 株)が ESC 耐性株であったことを明らかにした。また,/aewいがプラスミド間およびプラスミドと染色体間を ISEcplによって転移し,サルモネラの染色体または保有するプラスミド上に blamvが存在していたことを示した。食品従事者はblamnを保有するサルモネラを他のヒトへ伝播させ,さらに,サルモネラはプラスミドを介して bla遺伝子を他の細菌に水平伝播する可能性を示唆した。サルモネラに感染したヒトが数日から数か月間サルモネラを排出するため,食品従事者は薬剤耐性サルモネラおよび薬剤耐性因子のレゼルボアとなり得ることを示唆した。

本研究で,鶏肉,鶏卵生産に関連する採卵鶏生産環境および食品従事者に ESC 耐性サルモネラの分布状況を明らかにした。また,bla遺伝子の拡散に関わるプラスミドや ISを同定し,それらがり/遺伝子を保有する ESC 耐性サルモネラの出現・拡散に関与していることを示唆した。本研究により得られた知見は,ESC 耐性サルモネラの出現および拡散に関する基礎情報を提供し,今後の食品、環境,ヒトにおける ESC 耐性サルモネラの汚染実態調査の比較検討やbla遺伝子の拡散機序の解明のための重要な情報となる。

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